PMC:1448208 / 2104-40878 JSON TXT

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Id	Subject	Object	Predicate	Lexical cue
T24960	27133-27134	.	denotes	.
T24959	27130-27133	NN	denotes	SEM
T24958	27128-27129	SYM	denotes	-
T24957	27127-27128	HYPH	denotes	/
T24956	27126-27127	SYM	denotes	+
T24955	27121-27125	NN	denotes	mean
T24954	27117-27120	VBP	denotes	are
T24953	27110-27116	NNS	denotes	values
T24952	27106-27109	DT	denotes	All
T24951	27105-27134	sentence	denotes	All values are mean +/- SEM.
T24950	27104-27105	.	denotes	.
T24949	27101-27104	NN	denotes	age
T24948	27098-27100	IN	denotes	of
T24947	27092-27097	NNS	denotes	weeks
T24946	27089-27090	SYM	denotes	–
T24945	27090-27091	CD	denotes	6
T24944	27088-27089	CD	denotes	4
T24943	27083-27087	VBD	denotes	were
T24942	27078-27082	WDT	denotes	that
T24941	27073-27077	NNS	denotes	mice
T24497	25457-25460	NN	denotes	LAP
T24496	25453-25456	DT	denotes	the
T24495	25476-25486	NNS	denotes	transgenes
T24494	25448-25452	CC	denotes	both
T24493	25444-25447	IN	denotes	for
T24492	25435-25443	JJ	denotes	positive
T24491	25431-25434	CC	denotes	and
T24490	25428-25430	NN	denotes	E2
T24489	25417-25427	JJ	denotes	endogenous
T24482	25383-25384	-LRB-	denotes	(
T24481	25367-25373	NN	denotes	rescue
T24480	25374-25382	NN	denotes	genotype
T24479	25363-25366	DT	denotes	the
T24478	25359-25362	VBD	denotes	had
T24477	25354-25358	WDT	denotes	that
T24476	25347-25353	VBN	denotes	tested
T24475	25331-25341	JJ	denotes	transgenic
T24474	25342-25346	NN	denotes	line
T24473	25326-25330	DT	denotes	each
T24472	25321-25325	IN	denotes	from
T24471	25313-25320	VBG	denotes	weaning
T24470	25310-25312	IN	denotes	at
T24469	25304-25309	JJ	denotes	alive
T24468	25299-25303	NNS	denotes	mice
T24467	25296-25298	IN	denotes	of
T24466	25284-25295	NNS	denotes	percentages
T24465	25280-25283	VBP	denotes	are
T24464	25270-25279	VBN	denotes	Presented
T24463	25269-25488	sentence	denotes	Presented are percentages of mice alive at weaning from each transgenic line tested that had the rescue genotype (i.e., homozygous for knockout of endogenous E2 and positive for both the LAP-tTA and TRE-E2 transgenes).
T24462	25268-25269	.	denotes	.
T24461	25256-25262	NN	denotes	rescue
T24460	25263-25268	NNS	denotes	lines
T24459	25245-25255	JJ	denotes	transgenic
T24458	25242-25244	IN	denotes	of
T24457	25224-25232	NN	denotes	Survival
T24456	25222-25224	,	denotes	,
T24455	25233-25241	NN	denotes	analysis
T24454	25221-25222	LS	denotes	A
T24453	25220-25269	sentence	denotes	A, Survival analysis of transgenic rescue lines.
T24452	25219-25220	.	denotes	.
T24451	25207-25213	JJ	denotes	murine
T24450	25202-25206	NN	denotes	MSUD
T24449	25189-25201	JJ	denotes	intermediate
T24448	25214-25219	NN	denotes	model
T24447	25185-25188	DT	denotes	the
T24446	25182-25184	IN	denotes	of
T24445	25165-25181	NN	denotes	Characterization
T24940	27068-27072	IN	denotes	from
T24939	27053-27057	VBD	denotes	were
T24938	27058-27067	VBN	denotes	collected
T24937	27045-27052	NNS	denotes	Samples
T24936	27044-27105	sentence	denotes	Samples were collected from mice that were 4–6 weeks of age.
T24935	27043-27044	.	denotes	.
T24934	27026-27030	NN	denotes	mass
T24933	27031-27043	NN	denotes	spectrometry
T24932	27019-27025	JJ	denotes	tandem
T24931	27016-27018	IN	denotes	by
T24930	27005-27015	VBN	denotes	determined
T24929	27002-27004	IN	denotes	as
T24928	26993-27001	NNS	denotes	controls
T24927	26982-26992	NN	denotes	littermate
T24926	26978-26981	CC	denotes	and
T24925	26967-26971	NN	denotes	MSUD
T24924	26954-26966	JJ	denotes	intermediate
T24923	26972-26977	NN	denotes	model
T24922	26950-26953	DT	denotes	the
T24921	26947-26949	IN	denotes	in
T24920	26935-26939	NN	denotes	acid
T24919	26929-26934	NN	denotes	amino
T24918	26923-26928	NN	denotes	blood
T24917	26940-26946	NNS	denotes	levels
T24916	26912-26922	JJ	denotes	additional
T24915	26909-26911	IN	denotes	of
T24914	26901-26908	NN	denotes	Summary
T24680	26277-26287	VBN	denotes	sacrificed
T24679	26264-26276	RB	denotes	subsequently
T24678	26260-26263	CC	denotes	and
T24677	26251-26259	JJ	denotes	moribund
T24676	26241-26245	PRP	denotes	they
T24675	26246-26250	VBD	denotes	were
T24674	26235-26240	IN	denotes	until
T24673	26220-26224	VBD	denotes	were
T24672	26212-26219	NN	denotes	weaning
T24671	26209-26211	IN	denotes	at
T24670	26203-26208	JJ	denotes	alive
T24669	26225-26234	VBN	denotes	monitored
T24668	26198-26202	NNS	denotes	mice
T24667	26191-26197	NN	denotes	Rescue
T24666	26190-26322	sentence	denotes	Rescue mice alive at weaning were monitored until they were moribund and subsequently sacrificed or were found dead in their cages.
T24665	26189-26190	.	denotes	.
T24664	26185-26189	NN	denotes	525A
T24663	26181-26184	CC	denotes	and
T24662	26179-26180	NN	denotes	A
T24661	26173-26178	NNS	denotes	Lines
T24660	26168-26172	IN	denotes	from
T24659	26163-26167	NNS	denotes	mice
T24658	26159-26162	IN	denotes	for
T24657	26143-26151	NN	denotes	Survival
T24656	26141-26143	,	denotes	,
T24655	26152-26158	NNS	denotes	curves
T24654	26140-26141	LS	denotes	D
T24653	26139-26190	sentence	denotes	D, Survival curves for mice from Lines A and 525A.
T24652	26138-26139	.	denotes	.
T24651	26130-26131	SYM	denotes	≤
T24650	26128-26129	NN	denotes	P
T24649	26126-26128	,	denotes	,
T24648	26124-26126	SYM	denotes	**
T24647	26122-26123	:	denotes	;
T24646	26132-26138	CD	denotes	0.0001
T24645	26115-26116	SYM	denotes	≤
T24644	26113-26114	NN	denotes	P
T24643	26111-26113	,	denotes	,
T24642	26117-26122	CD	denotes	0.001
T24641	26110-26111	SYM	denotes	*
T24640	26109-26139	sentence	denotes	, P ≤ 0.001; *, P ≤ 0.0001.
T24639	26108-26109	.	denotes	.
T24638	26099-26103	NN	denotes	525A
T24637	26095-26098	CC	denotes	and
T24636	26093-26094	NN	denotes	A
T24635	26087-26092	NNS	denotes	Lines
T24634	26083-26086	CC	denotes	and
T24633	26104-26108	NNS	denotes	mice
T24632	26075-26082	NN	denotes	control
T24631	26072-26074	IN	denotes	of
T24630	26066-26071	NN	denotes	liver
T24629	26063-26065	IN	denotes	in
T24628	26047-26053	NN	denotes	enzyme
T24627	26041-26046	NN	denotes	BCKDH
T24626	26039-26041	,	denotes	,
T24625	26054-26062	NN	denotes	activity
T24624	26038-26039	LS	denotes	C
T24623	26037-26109	sentence	denotes	C, BCKDH enzyme activity in liver of control and Lines A and 525A mice.
T24622	26036-26037	.	denotes	.
T24621	26029-26030	SYM	denotes	<
T24620	26027-26028	NN	denotes	P
T24619	26025-26027	,	denotes	,
T24618	26023-26025	SYM	denotes	**
T24617	26021-26022	:	denotes	;
T24616	26031-26036	CD	denotes	0.005
T24615	26015-26016	SYM	denotes	≤
T24614	26013-26014	NN	denotes	P
T24613	26011-26013	,	denotes	,
T24612	26017-26021	CD	denotes	0.01
T24611	26010-26011	SYM	denotes	*
T24610	26009-26037	sentence	denotes	, P ≤ 0.01; *, P < 0.005.
T24609	26008-26009	.	denotes	.
T24608	26000-26008	VBN	denotes	analyzed
T24607	25992-25999	NNS	denotes	samples
T24606	25989-25991	IN	denotes	of
T24605	25981-25988	NNS	denotes	numbers
T24604	25977-25980	DT	denotes	the
T24603	25962-25966	NNS	denotes	bars
T24602	25958-25961	DT	denotes	the
T24601	25955-25957	IN	denotes	on
T24600	25967-25976	VBZ	denotes	indicates
T24599	25947-25954	NNS	denotes	numbers
T24598	25943-25946	DT	denotes	The
T24597	25942-26009	sentence	denotes	The numbers on the bars indicates the numbers of samples analyzed.
T24596	25941-25942	.	denotes	.
T24595	25935-25941	VBN	denotes	tested
T24594	25930-25934	NNS	denotes	ages
T24593	25926-25929	DT	denotes	all
T24592	25923-25925	IN	denotes	at
T24591	25914-25922	NNS	denotes	controls
T24590	25911-25913	IN	denotes	to
T24589	25902-25910	VBN	denotes	compared
T24588	25897-25901	NN	denotes	525A
T24587	25893-25896	CC	denotes	and
T24586	25891-25892	NN	denotes	A
T24585	25885-25890	NNS	denotes	Lines
T24584	25881-25884	IN	denotes	for
T24583	25873-25880	JJR	denotes	greater
T24582	25859-25872	RB	denotes	significantly
T24581	25854-25858	VBD	denotes	were
T24580	25847-25853	NNS	denotes	values
T24579	25838-25839	HYPH	denotes	/
T24578	25839-25846	NN	denotes	alanine
T24577	25834-25838	NN	denotes	BCAA
T24576	25833-25942	sentence	denotes	BCAA/alanine values were significantly greater for Lines A and 525A compared to controls at all ages tested.
T24575	25832-25833	.	denotes	.
T24574	25826-25832	NN	denotes	valine
T24573	25822-25825	CC	denotes	and
T24572	25820-25822	,	denotes	,
T24571	25810-25820	NN	denotes	isoleucine
T24570	25808-25810	,	denotes	,
T24569	25801-25808	NN	denotes	leucine
T24568	25798-25800	IN	denotes	of
T24567	25794-25797	NN	denotes	sum
T24566	25790-25793	DT	denotes	the
T24565	25780-25789	VBP	denotes	represent
T24564	25775-25779	NN	denotes	BCAA
T24563	25769-25774	JJ	denotes	Total
T24562	25768-25833	sentence	denotes	Total BCAA represent the sum of leucine, isoleucine, and valine.
T24561	25767-25768	.	denotes	.
T24560	25763-25767	NN	denotes	525A
T24559	25759-25762	CC	denotes	and
T24558	25757-25758	NN	denotes	A
T24557	25751-25756	NNS	denotes	Lines
T24556	25747-25750	CC	denotes	and
T24555	25738-25746	NNS	denotes	controls
T24554	25733-25737	IN	denotes	from
T24553	25728-25732	NNS	denotes	mice
T24552	25725-25727	IN	denotes	of
T24551	25719-25724	NN	denotes	blood
T24550	25716-25718	IN	denotes	in
T24549	25708-25715	NN	denotes	alanine
T24548	25705-25707	IN	denotes	to
T24547	25700-25704	NN	denotes	BCAA
T24546	25694-25699	JJ	denotes	total
T24545	25691-25693	IN	denotes	of
T24544	25683-25685	,	denotes	,
T24543	25685-25690	NN	denotes	Ratio
T24542	25682-25683	LS	denotes	B
T24541	25681-25768	sentence	denotes	B, Ratio of total BCAA to alanine in blood of mice from controls and Lines A and 525A.
T24540	25680-25681	.	denotes	.
T24539	25676-25680	NN	denotes	line
T24538	25671-25675	DT	denotes	each
T24537	25667-25670	IN	denotes	for
T24536	25654-25666	NNS	denotes	observations
T24535	25651-25653	IN	denotes	of
T24534	25643-25650	NNS	denotes	numbers
T24533	25639-25642	DT	denotes	the
T24532	25624-25628	NNS	denotes	bars
T24531	25620-25623	DT	denotes	the
T24530	25617-25619	IN	denotes	on
T24529	25629-25638	VBZ	denotes	indicates
T24528	25609-25616	NNS	denotes	numbers
T24527	25605-25608	DT	denotes	The
T24526	25604-25681	sentence	denotes	The numbers on the bars indicates the numbers of observations for each line.
T24525	25603-25604	.	denotes	.
T24524	25596-25603	NNS	denotes	animals
T24523	25593-25595	IN	denotes	of
T24522	25582-25592	NN	denotes	population
T24521	25577-25581	DT	denotes	this
T24520	25574-25576	IN	denotes	in
T24519	25562-25564	VBZ	denotes	is
T24518	25553-25561	NN	denotes	genotype
T24517	25548-25552	DT	denotes	this
T24516	25542-25547	WDT	denotes	which
T24515	25565-25573	VBN	denotes	expected
T24514	25539-25541	IN	denotes	at
T24513	25521-25528	JJ	denotes	maximum
T24512	25509-25520	JJ	denotes	theoretical
T24511	25529-25538	NN	denotes	frequency
T24510	25505-25508	DT	denotes	the
T24509	25494-25501	VBN	denotes	plotted
T24508	25502-25504	VBZ	denotes	is
T24507	25489-25493	RB	denotes	Also
T24506	25488-25604	sentence	denotes	Also plotted is the theoretical maximum frequency at which this genotype is expected in this population of animals.
T24505	25487-25488	.	denotes	.
T24504	25486-25487	-RRB-	denotes	)
T24503	25472-25473	HYPH	denotes	-
T24502	25473-25475	NN	denotes	E2
T24501	25469-25472	NN	denotes	TRE
T24500	25465-25468	CC	denotes	and
T24499	25460-25461	HYPH	denotes	-
T24498	25461-25464	NN	denotes	tTA
T24688	26321-26322	.	denotes	.
T23927	23007-23009	VB	denotes	be
T23926	23004-23006	TO	denotes	to
T23925	22999-23003	NN	denotes	lane
T23924	22994-22998	DT	denotes	each
T23923	22991-22993	IN	denotes	in
T23922	22984-22990	VBN	denotes	loaded
T23921	22976-22983	NN	denotes	protein
T23920	22973-22975	IN	denotes	of
T23919	23010-23018	VBN	denotes	compared
T23918	22966-22972	NN	denotes	amount
T23917	22960-22965	VB	denotes	allow
T23916	22957-22959	TO	denotes	to
T23915	22942-22947	NN	denotes	actin
T23914	22948-22956	NN	denotes	antibody
T23913	22939-22941	DT	denotes	an
T23912	22934-22938	IN	denotes	with
T23911	22919-22923	VBD	denotes	were
T23910	22924-22933	VBN	denotes	re-probed
T23909	22913-22918	NNS	denotes	blots
T23908	22909-22912	DT	denotes	All
T23907	22908-23019	sentence	denotes	All blots were re-probed with an actin antibody to allow amount of protein loaded in each lane to be compared.
T23906	22907-22908	.	denotes	.
T23905	22900-22907	NNS	denotes	tissues
T23904	22894-22899	DT	denotes	those
T23903	22891-22893	IN	denotes	in
T23902	22888-22890	NN	denotes	E2
T23901	22880-22887	VBN	denotes	derived
T23900	22870-22879	NN	denotes	transgene
T23899	22867-22869	IN	denotes	of
T23898	22859-22866	NNS	denotes	amounts
T23897	22848-22858	JJ	denotes	negligible
T23896	22837-22838	-RRB-	denotes	)
T23895	22836-22837	NN	denotes	E
T23894	22835-22836	-LRB-	denotes	(
T23893	22828-22834	NN	denotes	muscle
T23892	22824-22827	CC	denotes	and
T23891	22822-22824	,	denotes	,
T23890	22821-22822	-RRB-	denotes	)
T23889	22820-22821	NN	denotes	D
T23888	22819-22820	-LRB-	denotes	(
T23887	22812-22818	NN	denotes	kidney
T23886	22810-22812	,	denotes	,
T23885	22809-22810	-RRB-	denotes	)
T23884	22808-22809	NN	denotes	C
T23883	22807-22808	-LRB-	denotes	(
T23882	22801-22806	NN	denotes	brain
T23881	22798-22800	IN	denotes	of
T23880	22839-22847	VBD	denotes	revealed
T23879	22789-22797	NN	denotes	analysis
T23878	22784-22788	NN	denotes	blot
T23877	22776-22783	NNP	denotes	Western
T23876	22775-22908	sentence	denotes	Western blot analysis of brain (C), kidney (D), and muscle (E) revealed negligible amounts of transgene derived E2 in those tissues.
T23875	22774-22775	.	denotes	.
T23874	22766-22774	NNS	denotes	controls
T23873	22763-22765	IN	denotes	in
T23872	22759-22762	RB	denotes	not
T23871	22755-22758	CC	denotes	but
T23870	22750-22754	NNS	denotes	mice
T23869	22739-22749	JJ	denotes	transgenic
T23868	22736-22738	IN	denotes	in
T23867	22727-22732	JJ	denotes	human
T23866	22725-22727	,	denotes	,
T23865	22719-22725	VBN	denotes	tagged
T23864	22714-22715	HYPH	denotes	-
T23863	22715-22718	NN	denotes	myc
T23862	22713-22714	NN	denotes	c
T23861	22711-22713	,	denotes	,
T23860	22704-22711	VBN	denotes	derived
T23859	22694-22703	NN	denotes	transgene
T23858	22733-22735	NN	denotes	E2
T23857	22690-22693	DT	denotes	the
T23856	22687-22689	IN	denotes	of
T23855	22678-22686	NN	denotes	presence
T23854	22674-22677	DT	denotes	the
T23853	22651-22654	NN	denotes	tag
T23852	22646-22647	HYPH	denotes	-
T23851	22647-22650	NN	denotes	myc
T23850	22645-22646	NN	denotes	c
T23849	22655-22663	NN	denotes	antibody
T23848	22643-22644	DT	denotes	a
T23847	22638-22642	IN	denotes	with
T23846	22664-22673	VBD	denotes	confirmed
T23845	22629-22630	HYPH	denotes	-
T23844	22630-22637	NN	denotes	probing
T23843	22627-22629	NN	denotes	Re
T23842	22626-22775	sentence	denotes	Re-probing with a c-myc tag antibody confirmed the presence of the transgene derived, c-myc tagged, human E2 in transgenic mice but not in controls.
T23841	22625-22626	.	denotes	.
T23840	22618-22625	NNS	denotes	animals
T23839	22610-22617	NN	denotes	control
T23838	22607-22609	IN	denotes	in
T23837	22605-22606	-RRB-	denotes	)
T23836	22600-22602	CD	denotes	47
T23835	22599-22600	SYM	denotes	~
T23834	22598-22599	SYM	denotes	=
T23833	22596-22598	NN	denotes	MW
T23832	22603-22605	NN	denotes	Kd
T23831	22595-22596	-LRB-	denotes	(
T23830	22592-22594	NN	denotes	E2
T23829	22586-22591	NN	denotes	mouse
T23828	22583-22585	IN	denotes	of
T23827	22576-22582	NN	denotes	amount
T23826	22572-22575	DT	denotes	the
T23825	22569-22571	IN	denotes	to
T23824	22561-22568	JJ	denotes	similar
T23823	22550-22556	NN	denotes	amount
T23822	22546-22549	DT	denotes	the
T23821	22538-22545	NNS	denotes	animals
T23820	22534-22537	DT	denotes	the
T23819	22531-22533	IN	denotes	of
T23818	22526-22530	JJ	denotes	many
T23817	22557-22560	VBD	denotes	was
T23816	22523-22525	IN	denotes	in
T23815	22519-22522	CC	denotes	but
T23814	22510-22518	JJ	denotes	variable
T23813	22504-22505	NN	denotes	A
T23812	22500-22503	CD	denotes	525
T23811	22496-22499	CC	denotes	and
T23810	22494-22495	NN	denotes	A
T23809	22488-22493	NNS	denotes	Lines
T23808	22483-22487	IN	denotes	from
T23807	22478-22482	NNS	denotes	mice
T23806	22475-22477	IN	denotes	in
T23805	22473-22474	-RRB-	denotes	)
T23804	22471-22473	NN	denotes	Kd
T23803	22468-22470	CD	denotes	54
T23802	22467-22468	SYM	denotes	~
T23801	22454-22463	VBN	denotes	predicted
T23800	22464-22466	NN	denotes	MW
T23799	22453-22454	-LRB-	denotes	(
T23798	22442-22444	NN	denotes	E2
T23797	22445-22452	NN	denotes	protein
T23796	22436-22441	JJ	denotes	human
T23795	22433-22435	IN	denotes	of
T23794	22426-22432	NN	denotes	amount
T23793	22422-22425	DT	denotes	the
T23792	22506-22509	VBD	denotes	was
T23791	22417-22421	IN	denotes	that
T23790	22412-22416	VB	denotes	Note
T23789	22411-22626	sentence	denotes	Note that the amount of human E2 protein (predicted MW ~54 Kd) in mice from Lines A and 525 A was variable but in many of the animals the amount was similar to the amount of mouse E2 (MW=~47 Kd) in control animals.
T23788	22410-22411	.	denotes	.
T23787	22401-22405	NN	denotes	MSUD
T23786	22388-22400	JJ	denotes	intermediate
T23785	22384-22387	CC	denotes	and
T23784	22406-22410	NNS	denotes	mice
T23783	22376-22383	NN	denotes	control
T23782	22373-22375	IN	denotes	of
T23781	22367-22372	NN	denotes	liver
T23780	22364-22366	IN	denotes	in
T23779	22356-22363	NN	denotes	protein
T23778	22353-22355	NN	denotes	E2
T23777	22350-22352	IN	denotes	of
T23776	22336-22340	NN	denotes	blot
T23775	22328-22335	NNP	denotes	Western
T23774	22326-22328	,	denotes	,
T23773	22341-22349	NN	denotes	analysis
T23772	22325-22326	LS	denotes	B
T23771	22324-22411	sentence	denotes	B, Western blot analysis of E2 protein in liver of control and intermediate MSUD mice.
T23770	22323-22324	.	denotes	.
T23769	22319-22323	NNS	denotes	mice
T23768	22308-22318	JJ	denotes	transgenic
T23767	22305-22307	IN	denotes	of
T23766	22299-22304	NNS	denotes	lines
T23765	22291-22298	JJ	denotes	several
T23764	22284-22290	VB	denotes	create
T23763	22281-22283	TO	denotes	to
T23762	22272-22275	VBD	denotes	was
T23761	22276-22280	VBN	denotes	used
T23760	22262-22271	NN	denotes	construct
T23759	22257-22261	DT	denotes	This
T23758	22256-22324	sentence	denotes	This construct was used to create several lines of transgenic mice.
T23757	22255-22256	.	denotes	.
T23756	22231-22246	NN	denotes	polyadenylation
T23755	22247-22255	NN	denotes	sequence
T23754	22223-22230	VBN	denotes	derived
T23753	22218-22222	NN	denotes	SV40
T23752	22214-22217	CC	denotes	and
T23751	22212-22214	,	denotes	,
T23750	22201-22208	NN	denotes	epitope
T23749	22196-22197	HYPH	denotes	-
T23748	22197-22200	NN	denotes	myc
T23747	22195-22196	NN	denotes	c
T23746	22209-22212	NN	denotes	tag
T23745	22193-22194	DT	denotes	a
T23744	22191-22193	,	denotes	,
T23743	22177-22184	NN	denotes	alanine
T23742	22185-22191	NN	denotes	spacer
T23741	22174-22176	DT	denotes	an
T23740	22172-22174	,	denotes	,
T23739	22165-22167	NN	denotes	E2
T23738	22159-22164	JJ	denotes	human
T23737	22168-22172	NN	denotes	cDNA
T23736	22155-22158	DT	denotes	the
T23735	22153-22155	,	denotes	,
T23734	22152-22153	-RRB-	denotes	)
T23733	22143-22147	JJ	denotes	thin
T23732	22148-22152	NN	denotes	line
T23731	22142-22143	-LRB-	denotes	(
T23730	22125-22134	JJ	denotes	synthetic
T23729	22135-22141	NN	denotes	intron
T23728	22123-22124	DT	denotes	a
T23727	22121-22123	,	denotes	,
T23726	22113-22121	NN	denotes	promoter
T23725	22109-22112	DT	denotes	the
T23724	22106-22108	IN	denotes	of
T23723	22101-22105	NN	denotes	part
T23722	22098-22100	IN	denotes	as
T23721	22096-22097	-RRB-	denotes	)
T23720	22093-22096	NN	denotes	TRE
T23719	22092-22093	-LRB-	denotes	(
T23718	22075-22083	NN	denotes	response
T23717	22062-22074	NN	denotes	tetracycline
T23716	22084-22091	NN	denotes	element
T23715	22058-22061	DT	denotes	the
T23714	22049-22057	VBZ	denotes	contains
T23713	22035-22036	HYPH	denotes	-
T23712	22036-22038	NN	denotes	E2
T23711	22032-22035	NN	denotes	TRE
T23710	22039-22048	NN	denotes	transgene
T23709	22028-22031	DT	denotes	The
T23708	22027-22256	sentence	denotes	The TRE-E2 transgene contains the tetracycline response element (TRE) as part of the promoter, a synthetic intron (thin line), the human E2 cDNA, an alanine spacer, a c-myc epitope tag, and SV40 derived polyadenylation sequence.
T23707	22026-22027	.	denotes	.
T23706	22014-22017	NN	denotes	LAP
T23705	22005-22013	JJ	denotes	specific
T23704	21999-22004	NN	denotes	liver
T23703	22018-22026	NN	denotes	promoter
T23702	21995-21998	DT	denotes	the
T23701	21990-21994	IN	denotes	from
T23700	21988-21989	-RRB-	denotes	)
T23699	21985-21988	NN	denotes	tTA
T23698	21984-21985	-LRB-	denotes	(
T23697	21957-21958	HYPH	denotes	-
T23696	21958-21968	VBN	denotes	controlled
T23695	21945-21957	NN	denotes	tetracycline
T23694	21969-21983	NN	denotes	transactivator
T23693	21941-21944	DT	denotes	the
T23692	21933-21940	VBP	denotes	express
T23691	21928-21932	NNS	denotes	mice
T23690	21922-21927	DT	denotes	These
T23689	21921-22027	sentence	denotes	These mice express the tetracycline-controlled transactivator (tTA) from the liver specific LAP promoter.
T23688	21920-21921	.	denotes	.
T23687	21919-21920	-RRB-	denotes	]
T23686	21917-21919	CD	denotes	34
T23685	21916-21917	-LRB-	denotes	[
T23684	21895-21905	RB	denotes	previously
T23683	21890-21894	VBN	denotes	been
T23682	21885-21889	VBP	denotes	have
T23681	21906-21915	VBN	denotes	described
T23680	21869-21879	JJ	denotes	transgenic
T23679	21880-21884	NNS	denotes	mice
T23678	21864-21865	HYPH	denotes	-
T23677	21865-21868	NN	denotes	tTA
T23676	21861-21864	NN	denotes	LAP
T23675	21860-21921	sentence	denotes	LAP-tTA transgenic mice have been previously described [34].
T23674	21859-21860	.	denotes	.
T23673	21857-21859	NN	denotes	E2
T23672	21851-21856	JJ	denotes	human
T23671	21843-21850	VBP	denotes	express
T23670	21838-21842	WDT	denotes	that
T23669	21833-21837	NNS	denotes	mice
T23668	21825-21832	VB	denotes	produce
T23667	21822-21824	TO	denotes	to
T23666	21817-21821	VBN	denotes	used
T23665	21797-21807	JJ	denotes	Transgenic
T23664	21795-21797	,	denotes	,
T23663	21808-21816	NN	denotes	strategy
T23662	21794-21795	LS	denotes	A
T23661	21793-21860	sentence	denotes	A, Transgenic strategy used to produce mice that express human E2.
T23660	21792-21793	.	denotes	.
T23659	21776-21792	NN	denotes	characterization
T23658	21772-21775	CC	denotes	and
T23657	21755-21760	NN	denotes	mouse
T23656	21761-21771	NN	denotes	production
T23655	21744-21754	JJ	denotes	Transgenic
T21121	37050-37054	NN	denotes	MSUD
T21120	37037-37049	JJ	denotes	intermediate
T21119	37055-37060	NN	denotes	model
T21118	37033-37036	DT	denotes	the
T21117	37031-37033	,	denotes	,
T21112	37022-37024	CD	denotes	36
T21111	37021-37022	,	denotes	,
T21110	37019-37021	CD	denotes	35
T21109	37028-37030	CD	denotes	46
T21108	37018-37019	-LRB-	denotes	[
T21107	37008-37017	NNS	denotes	complexes
T21106	36996-37007	NN	denotes	multienzyme
T21105	36993-36995	IN	denotes	of
T21104	36984-36992	NN	denotes	analysis
T21103	36973-36983	JJ	denotes	structural
T21102	36970-36972	IN	denotes	in
T21101	36961-36969	NN	denotes	interest
T21100	36954-36960	JJ	denotes	recent
T21099	36951-36953	IN	denotes	of
T21098	37065-37072	VB	denotes	provide
T21097	36943-36950	IN	denotes	Because
T21096	36942-37127	sentence	denotes	Because of recent interest in structural analysis of multienzyme complexes [35,36,45,46], the intermediate MSUD model may provide a valuable resource for studies of structural biology.
T21095	36941-36942	.	denotes	.
T21094	36929-36934	JJ	denotes	whole
T21093	36935-36941	NN	denotes	animal
T21092	36925-36928	DT	denotes	the
T21091	36922-36924	IN	denotes	of
T21090	36916-36921	NN	denotes	level
T21089	36912-36915	DT	denotes	the
T21088	36909-36911	IN	denotes	at
T21087	36897-36901	NN	denotes	acid
T21086	36891-36896	NN	denotes	amino
T21085	36902-36908	NNS	denotes	levels
T21084	36885-36890	NN	denotes	blood
T21083	36881-36884	CC	denotes	and
T21082	36872-36880	NN	denotes	activity
T21081	36866-36871	NN	denotes	BCKDH
T21080	36863-36865	IN	denotes	to
T21079	36855-36862	NN	denotes	respect
T21078	36850-36854	IN	denotes	with
T21077	36842-36849	NN	denotes	thiamin
T21076	36839-36841	IN	denotes	of
T21075	36832-36838	NN	denotes	effect
T21074	36828-36831	DT	denotes	the
T21073	36823-36827	VB	denotes	test
T21072	36820-36822	TO	denotes	to
T21071	36814-36819	NN	denotes	model
T21070	36812-36813	DT	denotes	a
T21069	36792-36796	NN	denotes	MSUD
T21068	36779-36791	JJ	denotes	intermediate
T21067	36797-36802	NN	denotes	mouse
T21066	36775-36778	PRP$	denotes	our
T21065	36773-36775	,	denotes	,
T21064	36759-36764	JJR	denotes	newer
T21063	36765-36773	NNS	denotes	findings
T21062	36753-36758	DT	denotes	these
T21061	36750-36752	IN	denotes	of
T21060	36744-36749	NN	denotes	light
T21059	36803-36811	VBZ	denotes	provides
T21058	36741-36743	IN	denotes	In
T21057	36740-36942	sentence	denotes	In light of these newer findings, our intermediate MSUD mouse provides a model to test the effect of thiamin with respect to BCKDH activity and blood amino acid levels at the level of the whole animal.
T21056	36739-36740	.	denotes	.
T21340	37649-37653	NN	denotes	gene
T21339	37646-37648	IN	denotes	as
T21338	37641-37645	JJ	denotes	such
T21337	37639-37641	,	denotes	,
T21336	37617-37628	JJ	denotes	therapeutic
T21335	37629-37639	NNS	denotes	strategies
T21334	37611-37616	JJ	denotes	novel
T21333	37606-37610	VB	denotes	test
T21055	36738-36739	-RRB-	denotes	]
T21054	36735-36736	,	denotes	,
T21053	36733-36735	CD	denotes	45
T21052	36736-36738	CD	denotes	46
T21051	36732-36733	-LRB-	denotes	[
T21050	36714-36724	VBG	denotes	expressing
T21049	36711-36713	NN	denotes	E2
T21048	36725-36731	NN	denotes	allele
T21047	36701-36706	RBS	denotes	least
T21046	36707-36710	CD	denotes	one
T21045	36698-36700	RB	denotes	at
T21044	36695-36697	IN	denotes	of
T21043	36686-36694	NN	denotes	presence
T21042	36682-36685	DT	denotes	the
T21041	36677-36681	IN	denotes	upon
T21040	36667-36676	JJ	denotes	dependent
T21039	36642-36643	HYPH	denotes	-
T21038	36643-36653	JJ	denotes	responsive
T21037	36635-36642	NN	denotes	thiamin
T21036	36654-36663	NN	denotes	phenotype
T21035	36631-36634	DT	denotes	the
T21034	36664-36666	VBZ	denotes	is
T21033	36626-36630	IN	denotes	that
T21032	36611-36615	VBP	denotes	have
T21031	36605-36610	NNS	denotes	cells
T21030	36600-36604	NN	denotes	MSUD
T21029	36595-36599	IN	denotes	with
T21028	36616-36625	VBN	denotes	suggested
T21027	36579-36586	NN	denotes	culture
T21026	36574-36578	NN	denotes	cell
T21025	36587-36594	NNS	denotes	studies
T21024	36567-36573	JJ	denotes	Recent
T21023	36566-36740	sentence	denotes	Recent cell culture studies with MSUD cells have suggested that the thiamin-responsive phenotype is dependent upon the presence of at least one E2 expressing allele [45,46].
T21022	36565-36566	.	denotes	.
T21021	36564-36565	-RRB-	denotes	]
T21020	36563-36564	CD	denotes	1
T21019	36562-36563	-LRB-	denotes	[
T21018	36554-36561	NN	denotes	success
T21017	36546-36553	JJ	denotes	limited
T21016	36533-36536	VBZ	denotes	has
T21015	36527-36532	NNS	denotes	doses
T21014	36519-36526	NN	denotes	thiamin
T21013	36516-36518	IN	denotes	of
T21012	36505-36509	JJ	denotes	wide
T21011	36510-36515	NN	denotes	range
T21010	36503-36504	DT	denotes	a
T21009	36498-36502	IN	denotes	with
T21008	36537-36545	VBN	denotes	produced
T21007	36488-36497	NN	denotes	treatment
T21006	36484-36487	CC	denotes	and
T21005	36470-36483	JJ	denotes	heterogeneous
T21004	36458-36466	NNS	denotes	patients
T21003	36452-36457	DT	denotes	these
T21002	36449-36451	IN	denotes	of
T21001	36467-36469	VBZ	denotes	is
T21000	36439-36448	NN	denotes	phenotype
T20999	36435-36438	DT	denotes	The
T20998	36434-36566	sentence	denotes	The phenotype of these patients is heterogeneous and treatment with a wide range of thiamin doses has produced limited success [1].
T20997	36433-36434	.	denotes	.
T20996	36432-36433	-RRB-	denotes	]
T20995	36431-36432	CD	denotes	1
T20994	36430-36431	-LRB-	denotes	[
T20993	36415-36419	VBN	denotes	been
T20992	36411-36414	VBZ	denotes	has
T20991	36406-36410	NN	denotes	MSUD
T20990	36403-36405	IN	denotes	of
T20989	36420-36429	VBN	denotes	described
T20988	36386-36387	HYPH	denotes	-
T20987	36387-36397	JJ	denotes	responsive
T20986	36379-36386	NN	denotes	thiamin
T20985	36398-36402	NN	denotes	form
T20984	36377-36378	DT	denotes	A
T20983	36376-36434	sentence	denotes	A thiamin-responsive form of MSUD has been described [1].
T20982	36375-36376	.	denotes	.
T20981	36368-36375	NN	denotes	thiamin
T20980	36365-36367	IN	denotes	of
T20979	36358-36364	NN	denotes	effect
T20978	36354-36357	DT	denotes	the
T20977	36349-36353	VB	denotes	test
T20976	36346-36348	TO	denotes	to
T20975	36338-36345	NNS	denotes	studies
T20974	36334-36337	IN	denotes	for
T20973	36327-36333	JJ	denotes	useful
T20972	36319-36323	RB	denotes	also
T20971	36315-36318	MD	denotes	may
T20970	36304-36308	NN	denotes	MSUD
T20969	36291-36303	JJ	denotes	intermediate
T20968	36309-36314	NN	denotes	model
T20967	36287-36290	DT	denotes	the
T20966	36285-36287	,	denotes	,
T20965	36324-36326	VB	denotes	be
T20964	36273-36285	RB	denotes	Additionally
T20963	36272-36376	sentence	denotes	Additionally, the intermediate MSUD model may also be useful for studies to test the effect of thiamin.
T20962	36271-36272	.	denotes	.
T20961	36265-36271	NN	denotes	tissue
T20960	36257-36264	NN	denotes	autopsy
T20959	36254-36256	IN	denotes	on
T20958	36244-36248	MD	denotes	must
T20957	36249-36253	VB	denotes	rely
T20956	36238-36243	RB	denotes	often
T20955	36234-36237	CC	denotes	and
T20954	36232-36234	,	denotes	,
T20953	36217-36224	JJ	denotes	ethical
T20952	36225-36232	NNS	denotes	reasons
T20951	36209-36216	JJ	denotes	obvious
T20950	36205-36208	IN	denotes	for
T20949	36196-36204	NNS	denotes	patients
T20948	36190-36195	JJ	denotes	human
T20947	36187-36189	IN	denotes	in
T20946	36184-36186	VB	denotes	do
T20945	36181-36183	TO	denotes	to
T20944	36169-36170	HYPH	denotes	/
T20943	36170-36180	JJ	denotes	impossible
T20942	36160-36169	JJ	denotes	difficult
T20941	36155-36159	RB	denotes	very
T20940	36151-36154	VBP	denotes	are
T20939	36143-36150	NNS	denotes	studies
T20938	36138-36142	JJ	denotes	Such
T20937	36137-36272	sentence	denotes	Such studies are very difficult/impossible to do in human patients for obvious ethical reasons, and often must rely on autopsy tissue.
T20936	36136-36137	.	denotes	.
T20935	36129-36136	NN	denotes	disease
T20934	36125-36128	DT	denotes	the
T20933	36122-36124	IN	denotes	of
T20932	36092-36108	JJ	denotes	pathophysiologic
T20931	36081-36091	VBG	denotes	underlying
T20930	36109-36121	NNS	denotes	consequences
T20929	36077-36080	DT	denotes	the
T20928	36063-36076	VBG	denotes	investigating
T20927	36059-36062	IN	denotes	for
T20926	36052-36058	JJ	denotes	useful
T20925	36047-36051	RB	denotes	very
T20924	36039-36043	RB	denotes	also
T20923	36032-36038	MD	denotes	should
T20922	36025-36031	NNS	denotes	models
T20921	36019-36024	DT	denotes	these
T20920	36017-36019	,	denotes	,
T20919	36007-36017	NNS	denotes	treatments
T20918	35999-36006	JJ	denotes	various
T20917	35991-35998	VBG	denotes	testing
T20916	35988-35990	IN	denotes	to
T20915	35979-35987	NN	denotes	addition
T20914	36044-36046	VB	denotes	be
T20913	35976-35978	IN	denotes	In
T20912	35975-36137	sentence	denotes	In addition to testing various treatments, these models should also be very useful for investigating the underlying pathophysiologic consequences of the disease.
T20911	35974-35975	.	denotes	.
T20910	35968-35974	NNS	denotes	humans
T20909	35965-35967	IN	denotes	in
T20908	35957-35964	NNS	denotes	studies
T20907	35953-35956	IN	denotes	for
T20906	35949-35952	NN	denotes	way
T20905	35945-35948	DT	denotes	the
T20904	35940-35944	VB	denotes	pave
T20903	35934-35939	MD	denotes	could
T20902	35930-35933	CC	denotes	and
T20901	35907-35918	JJ	denotes	therapeutic
T20900	35919-35929	NNS	denotes	approaches
T20899	35902-35906	JJ	denotes	such
T20898	35894-35901	VB	denotes	advance
T20897	35891-35893	TO	denotes	to
T20895	35871-35878	NNS	denotes	studies
T20894	35864-35870	NN	denotes	animal
T20893	35859-35863	IN	denotes	with
T20892	35882-35890	VBN	denotes	expected
T20891	35851-35858	NN	denotes	Success
T20890	35850-35975	sentence	denotes	Success with animal studies is expected to advance such therapeutic approaches and could pave the way for studies in humans.
T20889	35849-35850	.	denotes	.
T20888	35843-35849	NN	denotes	safety
T20887	35837-35838	HYPH	denotes	-
T20886	35833-35837	JJ	denotes	long
T20885	35829-35832	CC	denotes	and
T20884	35827-35828	HYPH	denotes	-
T20883	35838-35842	NN	denotes	term
T20882	35822-35827	JJ	denotes	short
T20881	35817-35821	RB	denotes	also
T20880	35813-35816	CC	denotes	but
T20879	35811-35813	,	denotes	,
T20878	35799-35802	DT	denotes	the
T20877	35794-35798	RB	denotes	only
T20876	35803-35811	NN	denotes	efficacy
T20875	35790-35793	RB	denotes	not
T20874	35777-35789	VBG	denotes	establishing
T20873	35774-35776	IN	denotes	of
T20872	35755-35766	JJ	denotes	preliminary
T20871	35767-35773	NN	denotes	method
T20870	35753-35754	DT	denotes	a
T20869	35730-35735	NN	denotes	model
T20868	35723-35729	NN	denotes	animal
T20867	35736-35743	NNS	denotes	systems
T20866	35711-35722	JJ	denotes	appropriate
T20865	35708-35710	IN	denotes	on
T20864	35698-35707	NNS	denotes	therapies
T20863	35687-35691	NN	denotes	cell
T20862	35683-35686	CC	denotes	and
T20861	35692-35697	VBN	denotes	based
T20860	35678-35682	NN	denotes	gene
T20859	35675-35677	IN	denotes	of
T20858	35744-35752	VBZ	denotes	provides
T20857	35667-35674	NN	denotes	testing
T20856	35663-35666	DT	denotes	The
T20855	35662-35850	sentence	denotes	The testing of gene and cell based therapies on appropriate animal model systems provides a preliminary method of establishing not only the efficacy, but also short- and long-term safety.
T20854	35661-35662	.	denotes	.
T20853	35654-35661	NNS	denotes	studies
T20852	35642-35653	JJ	denotes	preclinical
T20851	35638-35641	IN	denotes	for
T20850	35629-35637	NNS	denotes	diseases
T20849	35621-35628	JJ	denotes	genetic
T20848	35618-35620	IN	denotes	of
T20847	35611-35617	NNS	denotes	models
T20846	35604-35610	NN	denotes	animal
T20845	35601-35603	IN	denotes	of
T20844	35596-35600	NN	denotes	need
T20843	35587-35595	JJ	denotes	critical
T20842	35583-35586	CC	denotes	and
T20841	35572-35582	NN	denotes	importance
T20840	35568-35571	DT	denotes	the
T20839	35551-35557	NNS	denotes	humans
T21116	37030-37031	-RRB-	denotes	]
T21115	37027-37028	,	denotes	,
T21114	37025-37027	CD	denotes	45
T21113	37024-37025	,	denotes	,
T20838	35548-35550	IN	denotes	in
T20837	35540-35547	NN	denotes	therapy
T20836	35535-35539	NN	denotes	gene
T20835	35530-35534	IN	denotes	with
T20834	35521-35529	NNS	denotes	problems
T20833	35514-35520	JJ	denotes	recent
T20832	35512-35514	,	denotes	,
T20831	35505-35512	NN	denotes	therapy
T20830	35500-35504	NN	denotes	gene
T20829	35497-35499	IN	denotes	to
T20828	35558-35567	VBP	denotes	highlight
T20827	35488-35496	JJ	denotes	Relevant
T20826	35487-35662	sentence	denotes	Relevant to gene therapy, recent problems with gene therapy in humans highlight the importance and critical need of animal models of genetic diseases for preclinical studies.
T20825	35486-35487	.	denotes	.
T20824	35485-35486	-RRB-	denotes	)
T20823	35484-35485	-RRB-	denotes	]
T20822	35482-35484	CD	denotes	44
T20821	35481-35482	-LRB-	denotes	[
T20820	35470-35474	NN	denotes	stem
T20819	35475-35480	NNS	denotes	cells
T20818	35460-35469	JJ	denotes	embryonic
T20817	35457-35459	CC	denotes	or
T20816	35455-35456	-RRB-	denotes	]
T20815	35452-35453	,	denotes	,
T20814	35450-35452	CD	denotes	42
T20813	35453-35455	CD	denotes	43
T20812	35449-35450	-LRB-	denotes	[
T20811	35435-35437	,	denotes	,
T20810	35431-35435	FW	denotes	e.g.
T20809	35437-35448	NNS	denotes	hepatocytes
T20808	35430-35431	-LRB-	denotes	(
T20807	35420-35429	NNS	denotes	therapies
T20806	35409-35413	NN	denotes	cell
T20805	35405-35408	CC	denotes	and
T20804	35403-35404	-RRB-	denotes	]
T20803	35401-35403	CD	denotes	41
T20802	35400-35401	SYM	denotes	-
T20801	35398-35400	CD	denotes	38
T20800	35397-35398	-LRB-	denotes	[
T20799	35414-35419	VBN	denotes	based
T20798	35392-35396	NN	denotes	gene
T20797	35389-35391	IN	denotes	as
T20796	35384-35388	JJ	denotes	such
T20795	35373-35383	NNS	denotes	treatments
T20794	35367-35372	JJ	denotes	novel
T20793	35362-35366	VB	denotes	test
T20792	35359-35361	TO	denotes	to
T20791	35343-35348	NN	denotes	mouse
T20790	35338-35342	NN	denotes	MSUD
T20789	35349-35355	NNS	denotes	models
T20788	35334-35337	DT	denotes	the
T20787	35331-35333	IN	denotes	by
T20786	35321-35330	VBN	denotes	presented
T20785	35356-35358	VBZ	denotes	is
T20784	35297-35308	JJ	denotes	significant
T20783	35292-35296	RBS	denotes	most
T20782	35309-35320	NN	denotes	opportunity
T20781	35288-35291	DT	denotes	The
T20780	35287-35487	sentence	denotes	The most significant opportunity presented by the MSUD mouse models is to test novel treatments such as gene [38-41] and cell based therapies (e.g., hepatocytes [42,43] or embryonic stem cells [44]).
T20779	35286-35287	.	denotes	.
T20778	35276-35281	JJ	denotes	human
T20777	35282-35286	NN	denotes	MSUD
T20776	35267-35275	VBG	denotes	modeling
T20775	35263-35266	IN	denotes	for
T20774	35251-35262	JJ	denotes	appropriate
T20773	35247-35250	CC	denotes	and
T20772	35241-35246	JJ	denotes	valid
T20771	35236-35240	RBR	denotes	more
T20770	35225-35231	NN	denotes	report
T20769	35220-35224	DT	denotes	this
T20768	35217-35219	IN	denotes	in
T20767	35207-35216	VBN	denotes	described
T20766	35193-35199	JJ	denotes	murine
T20765	35200-35206	NNS	denotes	models
T20764	35189-35192	DT	denotes	the
T20763	35187-35189	,	denotes	,
T20762	35179-35187	NN	denotes	contrast
T20761	35232-35235	VBP	denotes	are
T20760	35176-35178	IN	denotes	In
T20759	35175-35287	sentence	denotes	In contrast, the murine models described in this report are more valid and appropriate for modeling human MSUD.
T20758	35174-35175	.	denotes	.
T20757	35167-35174	NN	denotes	utility
T20756	35159-35166	JJ	denotes	limited
T20755	35156-35158	IN	denotes	of
T20754	35151-35155	RB	denotes	also
T20753	35142-35147	NN	denotes	model
T20752	35137-35141	DT	denotes	this
T20751	35135-35137	,	denotes	,
T20750	35134-35135	-RRB-	denotes	]
T20749	35133-35134	CD	denotes	1
T20748	35132-35133	-LRB-	denotes	[
T20747	35125-35131	NNS	denotes	humans
T20746	35120-35124	NN	denotes	MSUD
T20745	35116-35119	CC	denotes	and
T20744	35106-35109	NN	denotes	cow
T20743	35101-35105	NN	denotes	MSUD
T20742	35110-35115	NN	denotes	model
T20741	35097-35100	DT	denotes	the
T20740	35089-35096	IN	denotes	between
T20739	35077-35088	NNS	denotes	differences
T20738	35074-35076	IN	denotes	of
T20737	35062-35073	NN	denotes	observation
T20736	35058-35061	DT	denotes	the
T20735	35055-35057	IN	denotes	to
T20734	35051-35054	IN	denotes	due
T20733	35047-35050	CC	denotes	and
T20732	35034-35040	NN	denotes	animal
T20731	35028-35033	JJ	denotes	large
T20730	35026-35027	DT	denotes	a
T20729	35041-35046	NN	denotes	model
T20728	35021-35025	JJ	denotes	such
T20727	35018-35020	IN	denotes	by
T20726	35010-35017	VBN	denotes	imposed
T20725	34998-35009	NNS	denotes	constraints
T20724	34988-34997	JJ	denotes	practical
T20723	34985-34987	IN	denotes	to
T20722	34981-34984	IN	denotes	due
T20721	34979-34981	,	denotes	,
T20720	35148-35150	VBZ	denotes	is
T20719	34972-34979	RB	denotes	However
T20718	34971-35175	sentence	denotes	However, due to practical constraints imposed by such a large animal model and due to the observation of differences between the MSUD cow model and MSUD humans [1], this model is also of limited utility.
T20717	34970-34971	.	denotes	.
T20716	34969-34970	-RRB-	denotes	]
T20715	34967-34969	CD	denotes	19
T20714	34966-34967	SYM	denotes	-
T20713	34964-34966	CD	denotes	17
T20712	34963-34964	-LRB-	denotes	[
T20711	34942-34952	RB	denotes	previously
T20710	34937-34941	VBN	denotes	been
T20709	34932-34936	RB	denotes	also
T20708	34928-34931	VBZ	denotes	has
T20707	34923-34927	NN	denotes	MSUD
T20706	34920-34922	IN	denotes	of
T20705	34910-34913	NN	denotes	cow
T20704	34914-34919	NN	denotes	model
T20703	34908-34909	DT	denotes	a
T20702	34906-34908	,	denotes	,
T20701	34895-34900	NN	denotes	mouse
T20700	34901-34906	NN	denotes	model
T20699	34890-34894	DT	denotes	this
T20698	34887-34889	IN	denotes	to
T20697	34878-34886	NN	denotes	addition
T20696	34953-34962	VBN	denotes	described
T20695	34875-34877	IN	denotes	In
T20694	34874-34971	sentence	denotes	In addition to this mouse model, a cow model of MSUD has also been previously described [17-19].
T20693	34873-34874	.	denotes	.
T20692	34863-34873	NN	denotes	deficiency
T20691	34858-34862	NN	denotes	BCAT
T20690	34855-34857	IN	denotes	to
T20689	34847-34854	NN	denotes	disease
T20688	34842-34846	DT	denotes	this
T20687	34830-34841	VBG	denotes	attributing
T20686	34815-34819	VBN	denotes	been
T20685	34811-34814	VBZ	denotes	has
T20684	34806-34810	NN	denotes	MSUD
T20683	34803-34805	IN	denotes	of
T20682	34798-34802	NN	denotes	case
T20681	34795-34797	DT	denotes	no
T20680	34793-34795	,	denotes	,
T20674	34764-34769	NN	denotes	BCKDH
T20673	34761-34763	IN	denotes	of
T20672	34770-34773	VBP	denotes	are
T20671	34754-34760	NNS	denotes	levels
T20670	34750-34753	DT	denotes	the
T20669	34746-34749	CC	denotes	and
T20668	34740-34745	NN	denotes	BCKDH
T20667	34737-34739	IN	denotes	in
T20666	34733-34736	RB	denotes	not
T20665	34721-34729	NN	denotes	mutation
T20664	34717-34720	DT	denotes	the
T20663	34730-34732	VBZ	denotes	is
T20662	34709-34716	IN	denotes	because
T20661	34704-34708	NN	denotes	MSUD
T20660	34701-34703	IN	denotes	of
T20659	34690-34694	JJ	denotes	true
T20658	34695-34700	NN	denotes	model
T20657	34688-34689	DT	denotes	a
T20656	34684-34687	RB	denotes	not
T20655	34678-34680	PRP	denotes	it
T20654	34676-34678	,	denotes	,
T20653	34659-34670	JJ	denotes	interesting
T20652	34671-34676	NN	denotes	model
T20651	34656-34658	DT	denotes	an
T20650	34681-34683	VBZ	denotes	is
T20649	34648-34652	DT	denotes	this
T20648	34653-34655	VBZ	denotes	is
T20647	34642-34647	IN	denotes	While
T20646	34641-34781	sentence	denotes	While this is an interesting model, it is not a true model of MSUD because the mutation is not in BCKDH and the levels of BCKDH are normal.
T20645	34640-34641	.	denotes	.
T20644	34632-34640	JJ	denotes	elevated
T20643	34623-34631	RB	denotes	markedly
T20642	34606-34610	NN	denotes	BCAA
T20641	34600-34605	NN	denotes	blood
T20640	34611-34617	NNS	denotes	levels
T20639	34596-34599	DT	denotes	the
T20638	34589-34595	IN	denotes	though
T20637	34618-34622	VBD	denotes	were
T20636	34584-34588	RB	denotes	even
T20635	34577-34583	JJ	denotes	normal
T20634	34567-34572	NN	denotes	mouse
T20633	34562-34566	DT	denotes	this
T20632	34559-34561	IN	denotes	of
T20631	34552-34558	NN	denotes	muscle
T20630	34548-34551	CC	denotes	and
T20629	34542-34547	NN	denotes	liver
T20628	34538-34541	DT	denotes	the
T20627	34535-34537	IN	denotes	in
T20626	34573-34576	VBD	denotes	was
T20625	34520-34525	NN	denotes	BCKDH
T20624	34526-34534	NN	denotes	activity
T20623	34516-34519	DT	denotes	The
T20622	34515-34641	sentence	denotes	The BCKDH activity in the liver and muscle of this mouse was normal even though the blood BCAA levels were markedly elevated.
T20621	34514-34515	.	denotes	.
T20620	34513-34514	-RRB-	denotes	]
T20619	34511-34513	CD	denotes	20
T20618	34510-34511	-LRB-	denotes	[
T20896	35879-35881	VBZ	denotes	is
T20617	34500-34504	NN	denotes	BCAT
T20616	34486-34499	JJ	denotes	mitochondrial
T20615	34505-34509	NN	denotes	gene
T20614	34482-34485	DT	denotes	the
T20613	34471-34481	VBG	denotes	disrupting
T20612	34468-34470	IN	denotes	by
T20611	34449-34459	RB	denotes	previously
T20610	34445-34448	VBD	denotes	was
T20609	34440-34444	NN	denotes	MSUD
T20608	34434-34439	JJ	denotes	human
T20607	34423-34433	VBG	denotes	resembling
T20606	34460-34467	VBN	denotes	created
T20605	34413-34416	NN	denotes	ENU
T20604	34417-34422	NN	denotes	mouse
T20603	34410-34412	DT	denotes	An
T20602	34409-34515	sentence	denotes	An ENU mouse resembling human MSUD was previously created by disrupting the mitochondrial BCAT gene [20].
T20601	34408-34409	.	denotes	.
T20600	34392-34401	VBN	denotes	described
T20599	34381-34391	RB	denotes	previously
T20598	34402-34408	NNS	denotes	models
T20597	34377-34380	DT	denotes	the
T20596	34372-34376	IN	denotes	over
T20595	34363-34371	NNS	denotes	advances
T20594	34353-34362	JJ	denotes	important
T20593	34335-34348	NN	denotes	communication
T20592	34330-34334	DT	denotes	this
T20591	34327-34329	IN	denotes	in
T20590	34317-34326	VBN	denotes	described
T20589	34349-34352	VBP	denotes	are
T20588	34310-34316	NNS	denotes	models
T20587	34306-34309	DT	denotes	The
T20586	34305-34409	sentence	denotes	The models described in this communication are important advances over the previously described models.
T20585	34304-34305	.	denotes	.
T20584	34292-34294	VB	denotes	be
T20583	34287-34291	RB	denotes	also
T20582	34295-34304	VBN	denotes	regulated
T20581	34283-34286	MD	denotes	can
T20580	34279-34282	CC	denotes	and
T20579	34270-34278	NN	denotes	survival
T20578	34266-34269	IN	denotes	for
T20577	34260-34265	VBP	denotes	allow
T20576	34255-34259	WDT	denotes	that
T20575	34249-34254	NNS	denotes	lines
T20574	34244-34248	VB	denotes	find
T20573	34241-34243	TO	denotes	to
T20572	34231-34233	VB	denotes	be
T20571	34227-34230	MD	denotes	may
T20570	34221-34226	NNS	denotes	lines
T20569	34210-34220	JJ	denotes	additional
T20568	34207-34209	IN	denotes	of
T20567	34234-34240	VBN	denotes	needed
T20566	34197-34206	NN	denotes	Screening
T20565	34196-34305	sentence	denotes	Screening of additional lines may be needed to find lines that allow for survival and can also be regulated.
T20564	34195-34196	.	denotes	.
T20563	34185-34195	NN	denotes	expression
T20562	34175-34184	VBN	denotes	regulated
T20561	34171-34174	IN	denotes	for
T20560	34160-34170	JJ	denotes	permissive
T20559	34156-34159	RB	denotes	not
T20558	34141-34151	NNS	denotes	transgenes
T20557	34137-34140	DT	denotes	the
T20556	34134-34136	IN	denotes	of
T20555	34117-34128	NN	denotes	integration
T20554	34129-34133	NN	denotes	site
T20553	34113-34116	DT	denotes	the
T20552	34152-34155	VBD	denotes	was
T20551	34108-34112	IN	denotes	that
T20550	34096-34107	JJ	denotes	conceivable
T20549	34093-34095	VBZ	denotes	is
T20548	34090-34092	PRP	denotes	It
T20547	34089-34196	sentence	denotes	It is conceivable that the integration site of the transgenes was not permissive for regulated expression.
T20546	34088-34089	.	denotes	.
T20545	34081-34088	JJ	denotes	unknown
T20544	34066-34077	NN	denotes	doxycycline
T20543	34063-34065	IN	denotes	to
T20542	34050-34062	JJ	denotes	unresponsive
T20541	34045-34049	VBD	denotes	were
T20540	34035-34038	CD	denotes	two
T20539	34039-34044	NNS	denotes	lines
T20538	34029-34034	DT	denotes	these
T20537	34078-34080	VBZ	denotes	is
T20536	34022-34028	NN	denotes	reason
T20535	34018-34021	DT	denotes	The
T20534	34017-34089	sentence	denotes	The reason these two lines were unresponsive to doxycycline is unknown.
T20533	34016-34017	.	denotes	.
T20532	34015-34016	-RRB-	denotes	)
T20531	34006-34009	RB	denotes	not
T20530	34001-34005	NNS	denotes	data
T20529	34010-34015	VBN	denotes	shown
T20528	34000-34001	-LRB-	denotes	(
T20527	33993-33999	VBN	denotes	tested
T20526	33976-33986	JJ	denotes	transgenic
T20525	33972-33975	CD	denotes	two
T20524	33987-33992	NNS	denotes	lines
T20523	33968-33971	DT	denotes	the
T20522	33965-33967	IN	denotes	of
T20521	33958-33964	DT	denotes	either
T20520	33955-33957	IN	denotes	in
T20519	33943-33954	NN	denotes	doxycycline
T20518	33941-33943	,	denotes	,
T20517	33920-33932	NN	denotes	tetracycline
T20516	33913-33919	JJ	denotes	potent
T20515	33933-33941	NN	denotes	analogue
T20514	33909-33912	DT	denotes	the
T20513	33906-33908	IN	denotes	by
T20512	33886-33896	NN	denotes	expression
T20511	33883-33885	NN	denotes	E2
T20510	33877-33882	JJ	denotes	human
T20509	33897-33905	NN	denotes	cassette
T20508	33873-33876	DT	denotes	the
T20507	33869-33872	RP	denotes	off
T20506	33851-33863	RB	denotes	consistently
T20505	33864-33868	VB	denotes	turn
T20504	33848-33850	TO	denotes	to
T20503	33841-33847	JJ	denotes	unable
T20502	33833-33835	PRP	denotes	we
T20501	33831-33833	,	denotes	,
T20500	33836-33840	VBD	denotes	were
T20499	33824-33831	RB	denotes	However
T20498	33823-34017	sentence	denotes	However, we were unable to consistently turn off the human E2 expression cassette by the potent tetracycline analogue, doxycycline in either of the two transgenic lines tested (data not shown).
T20497	33822-33823	.	denotes	.
T20496	33804-33812	VBG	denotes	rescuing
T20495	33813-33822	NN	denotes	transgene
T20494	33800-33803	DT	denotes	the
T20493	33796-33799	RP	denotes	off
T20492	33788-33795	VBG	denotes	turning
T20491	33785-33787	IN	denotes	by
T20490	33771-33773	POS	denotes	's
T20489	33774-33784	NN	denotes	discretion
T20488	33759-33771	NN	denotes	investigator
T20487	33755-33758	DT	denotes	the
T20486	33752-33754	IN	denotes	at
T20485	33734-33741	JJ	denotes	classic
T20484	33742-33751	NN	denotes	phenotype
T20483	33730-33733	DT	denotes	the
T20482	33727-33729	IN	denotes	to
T20481	33714-33716	VB	denotes	be
T20480	33708-33713	MD	denotes	could
T20479	33717-33726	VBN	denotes	converted
T20478	33703-33707	WDT	denotes	that
T20477	33688-33692	NN	denotes	MSUD
T20476	33675-33687	JJ	denotes	intermediate
T20475	33693-33702	NN	denotes	phenotype
T20474	33672-33674	DT	denotes	an
T20473	33667-33671	IN	denotes	with
T20472	33662-33666	NNS	denotes	mice
T20471	33655-33661	VB	denotes	create
T20470	33652-33654	TO	denotes	to
T20469	33639-33647	NN	denotes	approach
T20468	33635-33638	PRP$	denotes	our
T20467	33628-33634	IN	denotes	behind
T20466	33648-33651	VBD	denotes	was
T20465	33619-33627	NN	denotes	strategy
T20464	33615-33618	DT	denotes	The
T20463	33614-33823	sentence	denotes	The strategy behind our approach was to create mice with an intermediate MSUD phenotype that could be converted to the classic phenotype at the investigator's discretion by turning off the rescuing transgene.
T20462	33613-33614	.	denotes	.
T20461	33612-33613	-RRB-	denotes	]
T20460	33610-33612	CD	denotes	34
T20459	33609-33610	-LRB-	denotes	[
T20448	33546-33549	VBZ	denotes	has
T20447	33555-33559	VBN	denotes	used
T20446	33541-33545	WDT	denotes	that
T20445	33527-33533	NN	denotes	switch
T20444	33522-33526	NN	denotes	gene
T20443	33512-33521	VBN	denotes	regulated
T20442	33499-33511	NN	denotes	tetracycline
T20441	33534-33540	NN	denotes	system
T20440	33495-33498	DT	denotes	the
T20439	33492-33494	IN	denotes	on
T20438	33482-33485	VBD	denotes	was
T20437	33471-33475	NN	denotes	MSUD
T20436	33458-33470	JJ	denotes	intermediate
T20435	33476-33481	NN	denotes	model
T20434	33454-33457	DT	denotes	the
T20433	33447-33453	VB	denotes	create
T20432	33444-33446	TO	denotes	to
T20431	33435-33438	VBD	denotes	was
T20430	33439-33443	VBN	denotes	used
T20429	33430-33434	WDT	denotes	that
T20428	33486-33491	VBN	denotes	based
T20427	33410-33420	JJ	denotes	transgenic
T20426	33421-33429	NN	denotes	approach
T20425	33406-33409	DT	denotes	The
T20424	33405-33614	sentence	denotes	The transgenic approach that was used to create the intermediate MSUD model was based on the tetracycline regulated gene switch system that has been used with great success in other studies, for example [34].
T20423	33404-33405	.	denotes	.
T20422	33400-33404	NN	denotes	MSUD
T20421	33397-33399	IN	denotes	of
T20420	33379-33391	JJ	denotes	intermediate
T20419	33392-33396	NN	denotes	form
T20418	33375-33378	DT	denotes	the
T20417	33372-33374	IN	denotes	of
T20416	33359-33365	NN	denotes	animal
T20415	33353-33358	JJ	denotes	small
T20414	33346-33352	JJ	denotes	useful
T20413	33366-33371	NN	denotes	model
T20412	33344-33345	DT	denotes	a
T20411	33318-33328	VBN	denotes	engineered
T20410	33306-33317	RB	denotes	genetically
T20409	33329-33333	NNS	denotes	mice
T20408	33300-33305	DT	denotes	these
T20407	33298-33300	,	denotes	,
T20406	33284-33289	JJ	denotes	human
T20405	33290-33298	NNS	denotes	patients
T20404	33280-33283	DT	denotes	the
T20403	33277-33279	IN	denotes	to
T20402	33265-33271	NN	denotes	rescue
T20401	33272-33276	NNS	denotes	mice
T20400	33261-33264	DT	denotes	the
T20399	33258-33260	IN	denotes	of
T20398	33234-33244	JJ	denotes	phenotypic
T20397	33245-33257	NNS	denotes	similarities
T20396	33230-33233	DT	denotes	the
T20395	33227-33229	IN	denotes	of
T20394	33334-33343	VBP	denotes	represent
T20393	33219-33226	IN	denotes	Because
T20392	33218-33405	sentence	denotes	Because of the phenotypic similarities of the rescue mice to the human patients, these genetically engineered mice represent a useful small animal model of the intermediate form of MSUD.
T20679	34820-34829	VBN	denotes	described
T20678	34782-34793	RB	denotes	Furthermore
T20677	34781-34874	sentence	denotes	Furthermore, no case of MSUD has been described attributing this disease to BCAT deficiency.
T20676	34780-34781	.	denotes	.
T20675	34774-34780	JJ	denotes	normal
T20391	33217-33218	.	denotes	.
T20390	33216-33217	-RRB-	denotes	]
T20389	33215-33216	CD	denotes	1
T20388	33214-33215	-LRB-	denotes	[
T20387	33207-33213	JJ	denotes	normal
T20386	33204-33206	IN	denotes	of
T20385	33202-33203	NN	denotes	%
T20384	33199-33200	SYM	denotes	–
T20383	33200-33202	CD	denotes	30
T20382	33198-33199	CD	denotes	3
T20381	33195-33197	IN	denotes	of
T20380	33189-33194	NN	denotes	range
T20379	33185-33188	DT	denotes	the
T20378	33182-33184	IN	denotes	in
T20377	33167-33172	NN	denotes	BCKDH
T20376	33163-33166	CC	denotes	and
T20375	33173-33181	NN	denotes	activity
T20374	33158-33162	NN	denotes	BCAA
T20373	33155-33157	IN	denotes	of
T20372	33148-33154	NNS	denotes	levels
T20371	33138-33147	VBN	denotes	increased
T20370	33125-33137	RB	denotes	persistently
T20369	33106-33111	JJ	denotes	human
T20368	33101-33105	NN	denotes	MSUD
T20367	33112-33120	NNS	denotes	patients
T20366	33088-33100	JJ	denotes	intermediate
T20365	33085-33087	IN	denotes	of
T20364	33121-33124	VBP	denotes	are
T20363	33075-33084	NNS	denotes	hallmarks
T20362	33071-33074	DT	denotes	The
T20361	33070-33218	sentence	denotes	The hallmarks of intermediate MSUD human patients are persistently increased levels of BCAA and BCKDH activity in the range of 3–30% of normal [1].
T20360	33069-33070	.	denotes	.
T20359	33060-33069	NNS	denotes	knockouts
T20358	33056-33059	CC	denotes	and
T20357	33047-33055	NNS	denotes	controls
T20356	33039-33046	IN	denotes	between
T20355	33026-33038	JJ	denotes	intermediate
T20354	33009-33015	NN	denotes	rescue
T20353	33016-33020	NNS	denotes	mice
T20352	33003-33008	DT	denotes	these
T20351	33000-33002	IN	denotes	of
T20350	32994-32999	NN	denotes	blood
T20349	32991-32993	IN	denotes	in
T20348	32984-32990	NNS	denotes	levels
T20347	32979-32983	NN	denotes	BCAA
T20346	33021-33025	VBD	denotes	were
T20345	32974-32978	IN	denotes	that
T20344	32956-32960	RB	denotes	also
T20343	32961-32973	VBD	denotes	demonstrated
T20342	32953-32955	PRP	denotes	We
T20341	32952-33070	sentence	denotes	We also demonstrated that BCAA levels in blood of these rescue mice were intermediate between controls and knockouts.
T20340	32951-32952	.	denotes	.
T20339	32943-32951	NN	denotes	survival
T20338	32937-32942	VB	denotes	allow
T20337	32934-32936	TO	denotes	to
T20336	32923-32933	JJ	denotes	sufficient
T20335	32913-32918	NN	denotes	liver
T20334	32909-32912	DT	denotes	the
T20333	32906-32908	IN	denotes	in
T20332	32891-32896	NN	denotes	BCKDH
T20331	32897-32905	NN	denotes	activity
T20330	32884-32890	JJ	denotes	normal
T20329	32881-32883	IN	denotes	of
T20328	32879-32880	NN	denotes	%
T20327	32877-32878	SYM	denotes	–
T20326	32876-32877	CD	denotes	5
T20325	32875-32876	SYM	denotes	~
T20324	32878-32879	CD	denotes	6
T20323	32870-32874	RB	denotes	only
T20322	32858-32863	NN	denotes	mouse
T20321	32864-32869	NNS	denotes	lines
T20320	32852-32857	DT	denotes	these
T20319	32849-32851	IN	denotes	in
T20318	32919-32922	VBD	denotes	was
T20317	32844-32848	IN	denotes	that
T20316	32839-32843	VB	denotes	note
T20315	32836-32838	TO	denotes	to
T20314	32824-32835	JJ	denotes	interesting
T20313	32821-32823	VBZ	denotes	is
T20312	32818-32820	PRP	denotes	It
T20311	32817-32952	sentence	denotes	It is interesting to note that in these mouse lines only ~5–6% of normal BCKDH activity in the liver was sufficient to allow survival.
T20310	32816-32817	.	denotes	.
T20309	32807-32816	NN	denotes	adulthood
T20308	32804-32806	IN	denotes	to
T20307	32783-32789	NN	denotes	rescue
T20306	32790-32794	NNS	denotes	mice
T20305	32779-32782	DT	denotes	the
T20304	32776-32778	IN	denotes	of
T20303	32795-32803	VBD	denotes	survived
T20302	32771-32775	JJ	denotes	Many
T20301	32770-32817	sentence	denotes	Many of the rescue mice survived to adulthood.
T20300	32769-32770	.	denotes	.
T20299	32751-32759	JJ	denotes	neonatal
T20298	32760-32769	NN	denotes	lethality
T20297	32747-32750	DT	denotes	the
T20296	32740-32746	VB	denotes	rescue
T20295	32737-32739	TO	denotes	to
T20294	32732-32736	JJ	denotes	able
T20293	32715-32723	NN	denotes	knockout
T20292	32724-32728	NNS	denotes	mice
T20291	32709-32714	DT	denotes	these
T20290	32706-32708	IN	denotes	of
T20289	32700-32705	NN	denotes	liver
T20288	32696-32699	DT	denotes	the
T20287	32693-32695	IN	denotes	in
T20286	32680-32682	NN	denotes	E2
T20285	32674-32679	JJ	denotes	human
T20284	32683-32692	NN	denotes	transgene
T20283	32672-32673	DT	denotes	a
T20282	32669-32671	IN	denotes	of
T20281	32658-32668	NN	denotes	expression
T20280	32729-32731	VBZ	denotes	is
T20279	32653-32657	IN	denotes	that
T20278	32648-32652	VBP	denotes	show
T20277	32645-32647	PRP	denotes	We
T20276	32644-32770	sentence	denotes	We show that expression of a human E2 transgene in the liver of these knockout mice is able to rescue the neonatal lethality.
T20275	32643-32644	.	denotes	.
T20274	32628-32636	JJ	denotes	neonatal
T20273	32622-32627	JJ	denotes	early
T20272	32637-32643	NN	denotes	period
T20271	32618-32621	DT	denotes	the
T20270	32611-32617	IN	denotes	during
T20269	32604-32606	NN	denotes	E2
T20268	32596-32603	VBN	denotes	derived
T20267	32586-32595	NN	denotes	transgene
T20266	32578-32585	IN	denotes	without
T20265	32568-32577	NNS	denotes	knockouts
T20264	32565-32567	NN	denotes	E2
T20263	32563-32565	,	denotes	,
T20262	32558-32563	RB	denotes	above
T20261	32607-32610	VBP	denotes	die
T20260	32548-32557	VBN	denotes	mentioned
T20259	32545-32547	IN	denotes	As
T20258	32544-32644	sentence	denotes	As mentioned above, E2 knockouts without transgene derived E2 die during the early neonatal period.
T20257	32543-32544	.	denotes	.
T20256	32530-32538	NN	denotes	knockout
T20255	32539-32543	NNS	denotes	mice
T20254	32527-32529	NN	denotes	E2
T20253	32524-32526	IN	denotes	of
T20252	32518-32523	NN	denotes	liver
T20251	32514-32517	DT	denotes	the
T20250	32511-32513	IN	denotes	in
T20249	32508-32510	NN	denotes	E2
T20248	32502-32507	JJ	denotes	human
T20247	32494-32501	VB	denotes	express
T20246	32491-32493	TO	denotes	to
T20245	32471-32481	JJ	denotes	transgenic
T20244	32482-32490	NN	denotes	strategy
T20243	32469-32470	DT	denotes	a
T20242	32461-32463	PRP	denotes	we
T20241	32459-32461	,	denotes	,
T20240	32455-32459	NN	denotes	MSUD
T20239	32442-32454	JJ	denotes	intermediate
T20238	32439-32441	IN	denotes	of
T20237	32433-32438	NN	denotes	model
T20236	32431-32432	DT	denotes	a
T20235	32464-32468	VBD	denotes	used
T20234	32424-32430	VB	denotes	create
T20233	32421-32423	TO	denotes	To
T20227	32393-32404	JJ	denotes	biochemical
T20226	32405-32415	NNS	denotes	phenotypes
T20225	32385-32392	JJ	denotes	several
T20224	32382-32384	IN	denotes	to
T20223	32374-32381	NN	denotes	respect
T20222	32369-32373	IN	denotes	with
T20221	32355-32360	JJ	denotes	human
T20220	32361-32368	NN	denotes	disease
T20219	32351-32354	DT	denotes	the
T20218	32348-32350	IN	denotes	of
T20217	32333-32341	JJ	denotes	faithful
T20216	32342-32347	NN	denotes	model
T20215	32331-32332	DT	denotes	a
T20214	32328-32330	VB	denotes	be
T20213	32325-32327	TO	denotes	to
T20212	32317-32324	VBZ	denotes	appears
T20211	32313-32316	CC	denotes	and
T20210	32308-32312	NN	denotes	MSUD
T20209	32300-32307	JJ	denotes	classic
T20208	32297-32299	IN	denotes	of
T20207	32291-32296	NN	denotes	model
T20206	32289-32290	DT	denotes	a
T20205	32267-32277	RB	denotes	accurately
T20204	32252-32260	NN	denotes	mutation
T20203	32247-32251	JJ	denotes	null
T20202	32261-32266	NN	denotes	mouse
T20201	32243-32246	DT	denotes	the
T20200	32241-32243	,	denotes	,
T20199	32238-32241	RB	denotes	far
T20198	32233-32237	RB	denotes	thus
T20197	32223-32232	VBN	denotes	completed
T20196	32198-32214	NN	denotes	characterization
T20195	32215-32222	NNS	denotes	studies
T20194	32194-32197	DT	denotes	the
T20193	32278-32288	VBZ	denotes	represents
T20192	32189-32193	IN	denotes	From
T20191	32188-32420	sentence	denotes	From the characterization studies completed thus far, the null mutation mouse accurately represents a model of classic MSUD and appears to be a faithful model of the human disease with respect to several biochemical phenotypes [1].
T20190	32187-32188	.	denotes	.
T20189	32169-32178	JJ	denotes	enzymatic
T20188	32179-32187	NN	denotes	activity
T20187	32163-32168	NN	denotes	BCKDH
T20186	32160-32162	IN	denotes	of
T20185	32155-32159	NN	denotes	half
T20184	32141-32154	RB	denotes	approximately
T20183	32134-32140	VBG	denotes	having
T20182	32126-32133	IN	denotes	despite
T20181	32121-32125	NN	denotes	BCAA
T20180	32118-32120	IN	denotes	of
T20179	32111-32117	NNS	denotes	levels
T20178	32104-32110	JJ	denotes	normal
T20177	32100-32103	VBD	denotes	had
T20176	32096-32099	CC	denotes	and
T20175	32089-32095	JJ	denotes	normal
T20174	32084-32088	VBD	denotes	were
T20173	32074-32083	NNS	denotes	knockouts
T20172	32061-32073	JJ	denotes	Heterozygous
T20171	32060-32188	sentence	denotes	Heterozygous knockouts were normal and had normal levels of BCAA despite having approximately half of BCKDH enzymatic activity.
T20458	33601-33608	NN	denotes	example
T20457	33597-33600	IN	denotes	for
T20456	33595-33597	,	denotes	,
T20455	33588-33595	NNS	denotes	studies
T20454	33582-33587	JJ	denotes	other
T20453	33579-33581	IN	denotes	in
T20452	33571-33578	NN	denotes	success
T20451	33565-33570	JJ	denotes	great
T20450	33560-33564	IN	denotes	with
T20449	33550-33554	VBN	denotes	been
T20170	32059-32060	.	denotes	.
T20169	32058-32059	-RRB-	denotes	]
T20168	32057-32058	CD	denotes	1
T20167	32056-32057	-LRB-	denotes	[
T20166	32042-32046	NN	denotes	MSUD
T20165	32047-32055	NNS	denotes	patients
T20164	32034-32041	JJ	denotes	classic
T20163	32031-32033	IN	denotes	in
T20162	32027-32030	CC	denotes	and
T20161	32025-32026	-RRB-	denotes	]
T20160	32023-32025	CD	denotes	17
T20159	32022-32023	-LRB-	denotes	[
T20158	32012-32016	NN	denotes	MSUD
T20157	32017-32021	NN	denotes	calf
T20156	32008-32011	DT	denotes	the
T20155	32005-32007	IN	denotes	in
T20154	31996-32004	VBN	denotes	observed
T20153	31993-31995	IN	denotes	as
T20152	31980-31992	NN	denotes	malnutrition
T20151	31976-31979	CC	denotes	and
T20150	31974-31976	,	denotes	,
T20149	31963-31974	NN	denotes	dehydration
T20148	31961-31963	,	denotes	,
T20147	31956-31961	NN	denotes	edema
T20146	31950-31955	NN	denotes	brain
T20145	31948-31950	,	denotes	,
T20144	31936-31948	NN	denotes	ketoacidosis
T20143	31934-31936	,	denotes	,
T20142	31928-31934	NNS	denotes	levels
T20141	31917-31927	JJ	denotes	neurotoxic
T20140	31914-31916	IN	denotes	to
T20139	31909-31913	NN	denotes	BCAA
T20138	31906-31908	IN	denotes	of
T20137	31893-31905	NN	denotes	accumulation
T20136	31889-31892	DT	denotes	the
T20135	31886-31888	IN	denotes	to
T20134	31882-31885	IN	denotes	due
T20133	31875-31881	RB	denotes	likely
T20132	31872-31874	VBZ	denotes	is
T20131	31853-31861	JJ	denotes	neonatal
T20130	31862-31871	NN	denotes	lethality
T20129	31848-31852	DT	denotes	This
T20128	31847-32060	sentence	denotes	This neonatal lethality is likely due to the accumulation of BCAA to neurotoxic levels, ketoacidosis, brain edema, dehydration, and malnutrition as observed in the MSUD calf [17] and in classic MSUD patients [1].
T20127	31846-31847	.	denotes	.
T20126	31841-31846	NN	denotes	birth
T20125	31838-31840	IN	denotes	of
T20124	31832-31837	NNS	denotes	hours
T20123	31829-31831	CD	denotes	72
T20122	31822-31828	IN	denotes	within
T20121	31801-31811	JJ	denotes	homozygous
T20120	31812-31816	NNS	denotes	pups
T20119	31797-31800	DT	denotes	the
T20118	31794-31796	IN	denotes	of
T20117	31790-31793	DT	denotes	all
T20116	31783-31789	RB	denotes	nearly
T20115	31781-31783	,	denotes	,
T20114	31817-31821	VBD	denotes	died
T20113	31774-31781	RB	denotes	Finally
T20112	31773-31847	sentence	denotes	Finally, nearly all of the homozygous pups died within 72 hours of birth.
T20111	31772-31773	.	denotes	.
T20110	31771-31772	-RRB-	denotes	]
T20109	31768-31769	,	denotes	,
T20108	31767-31768	CD	denotes	1
T20107	31769-31771	CD	denotes	37
T20106	31766-31767	-LRB-	denotes	[
T20105	31757-31765	NNS	denotes	patients
T20104	31754-31756	IN	denotes	in
T20103	31737-31753	NNS	denotes	encephalopathies
T20102	31732-31736	NN	denotes	MSUD
T20101	31728-31731	IN	denotes	for
T20100	31720-31727	NN	denotes	culprit
T20099	31716-31719	DT	denotes	the
T20098	31701-31704	VBP	denotes	are
T20097	31705-31715	VBN	denotes	considered
T20096	31695-31700	WDT	denotes	which
T20095	31693-31695	,	denotes	,
T20094	31682-31687	NN	denotes	amino
T20093	31670-31681	JJ	denotes	neuroactive
T20092	31662-31669	JJ	denotes	similar
T20091	31688-31693	NNS	denotes	acids
T20090	31656-31661	JJ	denotes	other
T20089	31652-31655	CC	denotes	and
T20088	31650-31652	,	denotes	,
T20087	31643-31650	NN	denotes	alanine
T20086	31641-31643	,	denotes	,
T20085	31632-31641	NN	denotes	glutamine
T20084	31630-31632	,	denotes	,
T20083	31621-31630	NN	denotes	glutamate
T20082	31618-31620	IN	denotes	of
T20081	31611-31617	NNS	denotes	levels
T20080	31603-31610	VBN	denotes	reduced
T20079	31598-31602	IN	denotes	from
T20078	31587-31590	MD	denotes	may
T20077	31591-31597	VB	denotes	result
T20076	31567-31577	JJ	denotes	neurologic
T20075	31578-31586	NNS	denotes	symptoms
T20074	31561-31566	DT	denotes	These
T20073	31560-31773	sentence	denotes	These neurologic symptoms may result from reduced levels of glutamate, glutamine, alanine, and other similar neuroactive amino acids, which are considered the culprit for MSUD encephalopathies in patients [1,37].
T20072	31559-31560	.	denotes	.
T20071	31558-31559	-RRB-	denotes	]
T20070	31557-31558	CD	denotes	1
T20069	31556-31557	-LRB-	denotes	[
T20068	31543-31555	NNS	denotes	difficulties
T20067	31531-31542	JJ	denotes	respiratory
T20066	31527-31530	CC	denotes	and
T20065	31525-31527	,	denotes	,
T20064	31517-31525	NN	denotes	activity
T20063	31511-31516	NN	denotes	motor
T20062	31508-31510	IN	denotes	of
T20061	31503-31507	NN	denotes	loss
T20060	31501-31503	,	denotes	,
T20059	31493-31501	NN	denotes	lethargy
T20058	31491-31493	,	denotes	,
T20057	31485-31491	NN	denotes	stupor
T20056	31483-31485	,	denotes	,
T20055	31475-31483	NNS	denotes	seizures
T20054	31472-31474	IN	denotes	as
T20053	31467-31471	JJ	denotes	such
T20052	31455-31466	NN	denotes	dysfunction
T20051	31444-31454	JJ	denotes	neurologic
T20050	31441-31443	IN	denotes	of
T20049	31435-31440	NNS	denotes	signs
T20048	31427-31434	VBP	denotes	include
T20047	31421-31426	DT	denotes	These
T20046	31420-31560	sentence	denotes	These include signs of neurologic dysfunction such as seizures, stupor, lethargy, loss of motor activity, and respiratory difficulties [1].
T20045	31419-31420	.	denotes	.
T20044	31406-31410	NN	denotes	MSUD
T20043	31398-31405	JJ	denotes	classic
T20042	31411-31419	NNS	denotes	patients
T20041	31390-31397	JJ	denotes	newborn
T20040	31387-31389	IN	denotes	in
T20039	31382-31386	VBN	denotes	seen
T20038	31373-31381	NNS	denotes	symptoms
T20037	31352-31357	NN	denotes	mouse
T20036	31358-31362	NNS	denotes	pups
T20035	31341-31351	JJ	denotes	homozygous
T20034	31338-31340	IN	denotes	of
T20033	31363-31372	VBZ	denotes	resembles
T20032	31318-31328	JJ	denotes	phenotypic
T20031	31329-31337	NN	denotes	behavior
T20030	31314-31317	DT	denotes	The
T20029	31313-31420	sentence	denotes	The phenotypic behavior of homozygous mouse pups resembles symptoms seen in newborn classic MSUD patients.
T20028	31312-31313	.	denotes	.
T20027	31308-31312	NNS	denotes	pups
T20026	31297-31307	JJ	denotes	homozygous
T20025	31294-31296	IN	denotes	of
T20024	31282-31293	NNS	denotes	fibroblasts
T20023	31278-31281	CC	denotes	and
T20022	31272-31277	NN	denotes	liver
T20021	31269-31271	IN	denotes	in
T20020	31262-31268	JJ	denotes	absent
T20019	31258-31261	VBD	denotes	was
T20018	31247-31249	NN	denotes	E2
T20017	31250-31257	NN	denotes	protein
T20016	31232-31246	JJ	denotes	Immunoreactive
T20015	31231-31313	sentence	denotes	Immunoreactive E2 protein was absent in liver and fibroblasts of homozygous pups.
T20014	31230-31231	.	denotes	.
T20013	31226-31230	NN	denotes	BCAA
T20012	31212-31225	JJ	denotes	unmetabolized
T19940	30835-30840	NN	denotes	birth
T19939	30832-30834	IN	denotes	at
T19938	30825-30831	JJ	denotes	normal
T19937	30816-30824	VBD	denotes	appeared
T19936	30812-30815	CC	denotes	and
T19935	30793-30801	VBN	denotes	expected
T19934	30802-30811	NN	denotes	frequency
T19933	30789-30792	DT	denotes	the
T19932	30786-30788	IN	denotes	at
T19931	30776-30780	VBD	denotes	were
T19930	30781-30785	VBN	denotes	born
T19929	30771-30775	NNS	denotes	mice
T19928	30762-30770	NN	denotes	Knockout
T19927	30761-30841	sentence	denotes	Knockout mice were born at the expected frequency and appeared normal at birth.
T19926	30760-30761	.	denotes	.
T19925	30756-30760	NN	denotes	MSUD
T19924	30748-30755	JJ	denotes	classic
T19923	30743-30747	IN	denotes	with
T19922	30736-30742	NNS	denotes	humans
T19921	30733-30735	IN	denotes	to
T19920	30725-30732	JJ	denotes	similar
T19919	30714-30724	RB	denotes	strikingly
T19918	30694-30702	NN	denotes	knockout
T19917	30703-30710	NNS	denotes	animals
T19916	30688-30693	DT	denotes	these
T19915	30685-30687	IN	denotes	of
T19914	30711-30713	VBZ	denotes	is
T19913	30675-30684	NN	denotes	phenotype
T19912	30671-30674	DT	denotes	The
T19911	30670-30761	sentence	denotes	The phenotype of these knockout animals is strikingly similar to humans with classic MSUD.
T19910	30669-30670	.	denotes	.
T19909	30664-30669	NN	denotes	BCKDH
T19908	30661-30663	IN	denotes	of
T19907	30650-30652	NN	denotes	E2
T19906	30653-30660	NN	denotes	subunit
T19905	30646-30649	DT	denotes	the
T19904	30643-30645	IN	denotes	of
T19903	30634-30642	NN	denotes	knockout
T19902	30629-30633	NN	denotes	gene
T19901	30626-30628	IN	denotes	by
T19900	30614-30617	VBD	denotes	was
T19899	30609-30613	NN	denotes	MSUD
T19898	30601-30608	JJ	denotes	classic
T19897	30598-30600	IN	denotes	of
T19896	30618-30625	VBN	denotes	created
T19895	30592-30597	NN	denotes	model
T19894	30588-30591	PRP$	denotes	Our
T19893	30587-30670	sentence	denotes	Our model of classic MSUD was created by gene knockout of the E2 subunit of BCKDH.
T19892	30586-30587	.	denotes	.
T19891	30579-30586	NN	denotes	disease
T19890	30575-30578	DT	denotes	the
T19889	30572-30574	IN	denotes	of
T19888	30553-30565	JJ	denotes	intermediate
T19887	30549-30552	CC	denotes	and
T19886	30541-30548	JJ	denotes	classic
T19885	30566-30571	NNS	denotes	forms
T19884	30537-30540	DT	denotes	the
T20232	32420-32544	sentence	denotes	To create a model of intermediate MSUD, we used a transgenic strategy to express human E2 in the liver of E2 knockout mice.
T20231	32419-32420	.	denotes	.
T20230	32418-32419	-RRB-	denotes	]
T20229	32417-32418	CD	denotes	1
T20228	32416-32417	-LRB-	denotes	[
T19883	30532-30536	IN	denotes	with
T19882	30523-30531	NNS	denotes	patients
T19881	30518-30522	NN	denotes	MSUD
T19880	30515-30517	IN	denotes	to
T19879	30507-30514	JJ	denotes	similar
T19878	30502-30506	RB	denotes	very
T19877	30487-30501	RB	denotes	phenotypically
T19876	30483-30486	VBP	denotes	are
T19875	30478-30482	WDT	denotes	that
T19874	30465-30470	NN	denotes	mouse
T19873	30454-30464	VBN	denotes	engineered
T19872	30442-30453	RB	denotes	genetically
T19871	30471-30477	NNS	denotes	models
T19870	30438-30441	CD	denotes	two
T19869	30435-30437	IN	denotes	of
T19868	30418-30434	NN	denotes	characterization
T19867	30414-30417	CC	denotes	and
T19866	30402-30413	NN	denotes	development
T19865	30398-30401	DT	denotes	the
T19864	30386-30388	PRP	denotes	we
T19863	30384-30386	,	denotes	,
T19862	30378-30384	NN	denotes	report
T19861	30373-30377	DT	denotes	this
T19860	30389-30397	VBP	denotes	describe
T19859	30370-30372	IN	denotes	In
T19858	30369-30587	sentence	denotes	In this report, we describe the development and characterization of two genetically engineered mouse models that are phenotypically very similar to MSUD patients with the classic and intermediate forms of the disease.
T19857	30368-30369	.	denotes	.
T19856	30355-30359	VBN	denotes	been
T19855	30351-30354	RB	denotes	now
T19854	30347-30350	VBZ	denotes	has
T19853	30360-30368	VBN	denotes	overcome
T19852	30340-30346	NN	denotes	hurdle
T19851	30335-30339	DT	denotes	This
T19850	30334-30369	sentence	denotes	This hurdle has now been overcome.
T19849	30333-30334	.	denotes	.
T19848	30326-30333	NN	denotes	disease
T19847	30322-30325	DT	denotes	the
T19846	30319-30321	IN	denotes	of
T19845	30306-30312	NN	denotes	animal
T19844	30297-30305	JJ	denotes	accurate
T19843	30295-30297	,	denotes	,
T19842	30286-30295	JJ	denotes	practical
T19841	30313-30318	NN	denotes	model
T19840	30284-30285	DT	denotes	a
T19839	30281-30283	IN	denotes	of
T19838	30276-30280	NN	denotes	lack
T19837	30272-30275	DT	denotes	the
T19836	30263-30266	VBZ	denotes	has
T19835	30258-30262	NN	denotes	MSUD
T19834	30254-30257	IN	denotes	for
T19833	30243-30253	NNS	denotes	treatments
T19832	30239-30242	JJ	denotes	new
T19831	30228-30238	VBG	denotes	developing
T19830	30225-30227	IN	denotes	in
T19829	30267-30271	VBN	denotes	been
T19828	30212-30217	JJ	denotes	major
T19827	30218-30224	NN	denotes	hurdle
T19826	30210-30211	DT	denotes	A
T20011	31209-31211	IN	denotes	of
T20010	31196-31208	NN	denotes	accumulation
T20009	31192-31195	DT	denotes	the
T20008	31188-31191	IN	denotes	for
T20007	31177-31187	VBG	denotes	accounting
T20006	31175-31177	,	denotes	,
T20005	31163-31175	JJ	denotes	undetectable
T20004	31148-31153	NN	denotes	mouse
T20003	31154-31158	NNS	denotes	pups
T20002	31139-31147	NN	denotes	knockout
T20001	31128-31138	JJ	denotes	homozygous
T20000	31125-31127	IN	denotes	of
T19999	31118-31124	NNS	denotes	livers
T19998	31115-31117	IN	denotes	in
T19997	31109-31114	NN	denotes	BCKDH
T19996	31106-31108	IN	denotes	of
T19995	31159-31162	VBD	denotes	was
T19994	31097-31105	NN	denotes	activity
T19993	31093-31096	DT	denotes	The
T19992	31092-31231	sentence	denotes	The activity of BCKDH in livers of homozygous knockout mouse pups was undetectable, accounting for the accumulation of unmetabolized BCAA.
T19991	31091-31092	.	denotes	.
T19990	31090-31091	-RRB-	denotes	)
T19989	31089-31090	CD	denotes	1
T19988	31083-31088	NN	denotes	Table
T19987	31082-31083	-LRB-	denotes	(
T19986	31067-31071	VBD	denotes	were
T19985	31065-31067	,	denotes	,
T19984	31061-31065	NN	denotes	BCAA
T19983	31058-31060	IN	denotes	of
T19982	31047-31057	NN	denotes	metabolism
T19981	31040-31046	JJ	denotes	normal
T19980	31035-31039	IN	denotes	with
T19979	31025-31027	VBZ	denotes	is
T19978	31028-31034	VBN	denotes	linked
T19977	31015-31024	NN	denotes	synthesis
T19976	31009-31014	WP$	denotes	whose
T19975	31007-31009	,	denotes	,
T19974	30998-31007	NN	denotes	glutamine
T19973	30994-30997	CC	denotes	and
T19972	30992-30994	,	denotes	,
T19971	30983-30992	NN	denotes	glutamate
T19970	30981-30983	,	denotes	,
T19969	30974-30981	NN	denotes	alanine
T19968	30962-30967	NN	denotes	amino
T19967	30968-30973	NNS	denotes	acids
T19966	30958-30961	DT	denotes	the
T19965	30955-30957	IN	denotes	of
T19964	30948-30954	NNS	denotes	levels
T19963	30946-30948	,	denotes	,
T19962	31072-31081	VBN	denotes	decreased
T19961	30933-30946	RB	denotes	Concomitantly
T19960	30932-31092	sentence	denotes	Concomitantly, levels of the amino acids alanine, glutamate, and glutamine, whose synthesis is linked with normal metabolism of BCAA, were decreased (Table 1).
T19959	30931-30932	.	denotes	.
T19958	30923-30931	JJ	denotes	elevated
T19957	30914-30922	RB	denotes	markedly
T19956	30904-30908	NN	denotes	BCAA
T19955	30901-30903	IN	denotes	of
T19954	30894-30900	NNS	denotes	levels
T19953	30888-30893	NN	denotes	blood
T19952	30886-30888	,	denotes	,
T19951	30878-30886	NN	denotes	suckling
T19950	30868-30877	VBG	denotes	following
T19949	30864-30867	CC	denotes	and
T19948	30858-30863	NN	denotes	birth
T19947	30855-30857	IN	denotes	of
T19946	30851-30854	NN	denotes	day
T19945	30849-30850	DT	denotes	a
T19944	30909-30913	VBD	denotes	were
T19943	30842-30848	IN	denotes	Within
T19942	30841-30932	sentence	denotes	Within a day of birth and following suckling, blood levels of BCAA were markedly elevated.
T19941	30840-30841	.	denotes	.
T16742	28868-28869	-LRB-	denotes	[
T16825	29245-29246	.	denotes	.
T16824	29238-29245	NNS	denotes	tissues
T16823	29232-29237	DT	denotes	those
T16822	29229-29231	IN	denotes	in
T16821	29218-29228	JJ	denotes	negligible
T16820	29212-29214	NN	denotes	E2
T16819	29209-29211	IN	denotes	of
T16818	29198-29208	NN	denotes	expression
T16817	29196-29198	,	denotes	,
T16816	29184-29196	RB	denotes	respectively
T16815	29181-29183	NN	denotes	3E
T16814	29177-29180	CC	denotes	and
T16813	29175-29176	NN	denotes	D
T16812	29173-29175	,	denotes	,
T16811	29171-29173	NN	denotes	3C
T16810	29164-29170	NN	denotes	Figure
T16809	29161-29163	IN	denotes	in
T16808	29215-29217	VBZ	denotes	is
T16807	29155-29160	VBN	denotes	shown
T16806	29152-29154	IN	denotes	As
T16805	29151-29246	sentence	denotes	As shown in Figure 3C, D and 3E respectively, expression of E2 is negligible in those tissues.
T16804	29150-29151	.	denotes	.
T16803	29144-29150	NN	denotes	muscle
T16802	29140-29143	CC	denotes	and
T16801	29133-29139	NN	denotes	kidney
T16800	29131-29133	,	denotes	,
T16799	29126-29131	NN	denotes	brain
T16798	29123-29125	IN	denotes	in
T16797	29110-29112	NN	denotes	E2
T16796	29113-29122	NN	denotes	transgene
T16795	29106-29109	DT	denotes	the
T16794	29103-29105	IN	denotes	of
T16793	29092-29102	NN	denotes	expression
T16792	29084-29091	VB	denotes	analyze
T16791	29081-29083	TO	denotes	to
T16790	29072-29080	NN	denotes	analysis
T16789	29067-29071	NN	denotes	blot
T16788	29059-29066	NNP	denotes	western
T16787	29049-29053	RB	denotes	also
T16786	29054-29058	VBD	denotes	used
T16785	29046-29048	PRP	denotes	We
T16784	29045-29151	sentence	denotes	We also used western blot analysis to analyze expression of the E2 transgene in brain, kidney and muscle.
T16783	29044-29045	.	denotes	.
T16782	29034-29038	NN	denotes	acid
T16781	29028-29033	NN	denotes	amino
T16780	29039-29044	NN	denotes	level
T16779	29024-29027	DT	denotes	the
T16778	29021-29023	IN	denotes	at
T16777	29018-29020	NN	denotes	E2
T16776	29012-29017	NN	denotes	mouse
T16775	29009-29011	IN	denotes	to
T16774	29000-29008	NN	denotes	identity
T16773	28998-28999	NN	denotes	%
T16772	28996-28998	CD	denotes	88
T16771	28995-28996	SYM	denotes	~
T16770	28988-28994	VBZ	denotes	shares
T16769	28985-28987	NN	denotes	E2
T16768	28979-28984	JJ	denotes	Human
T16767	28978-29045	sentence	denotes	Human E2 shares ~88% identity to mouse E2 at the amino acid level.
T16766	28977-28978	.	denotes	.
T16765	28969-28977	NNS	denotes	subunits
T16764	28966-28968	NN	denotes	E3
T16763	28962-28965	CC	denotes	and
T16762	28959-28961	NN	denotes	E1
T16761	28953-28958	NN	denotes	mouse
T16760	28948-28952	IN	denotes	with
T16759	28938-28947	VBN	denotes	complexed
T16758	28933-28937	WRB	denotes	when
T16757	28922-28932	JJ	denotes	functional
T16756	28916-28921	RB	denotes	fully
T16755	28912-28915	RB	denotes	not
T16754	28905-28907	NN	denotes	E2
T16753	28899-28904	JJ	denotes	human
T16752	28908-28911	VBD	denotes	was
T16751	28894-28898	IN	denotes	that
T16750	28885-28893	JJ	denotes	possible
T16749	28880-28884	RB	denotes	also
T16748	28877-28879	VBZ	denotes	is
T16747	28874-28876	PRP	denotes	It
T16746	28873-28978	sentence	denotes	It is also possible that human E2 was not fully functional when complexed with mouse E1 and E3 subunits.
T16745	28872-28873	.	denotes	.
T16744	28871-28872	-RRB-	denotes	]
T16743	28869-28871	CD	denotes	36
T16741	28851-28858	NN	denotes	subunit
T16740	28859-28867	NN	denotes	assembly
T16739	28844-28850	JJ	denotes	normal
T16738	28839-28843	IN	denotes	with
T16737	28815-28819	FW	denotes	coli
T16736	28812-28814	FW	denotes	E.
T16735	28802-28811	JJ	denotes	analogous
T16734	28820-28827	NN	denotes	subunit
T16733	28799-28801	DT	denotes	an
T16732	28796-28798	IN	denotes	of
T16731	28779-28786	NN	denotes	carboxy
T16730	28787-28795	NN	denotes	terminus
T16729	28775-28778	DT	denotes	the
T16728	28772-28774	IN	denotes	on
T16727	28762-28767	NN	denotes	Hisx6
T16726	28768-28771	NN	denotes	tag
T16725	28760-28761	DT	denotes	a
T16724	28757-28759	IN	denotes	of
T16723	28828-28838	VBD	denotes	interfered
T16722	28747-28756	NN	denotes	insertion
T16721	28743-28746	CC	denotes	and
T16720	28741-28742	-RRB-	denotes	]
T16719	28739-28741	CD	denotes	35
T16718	28738-28739	-LRB-	denotes	[
T16717	28725-28737	NNS	denotes	interactions
T16716	28717-28724	NN	denotes	subunit
T16715	28713-28716	IN	denotes	for
T16714	28703-28712	JJ	denotes	essential
T16713	28678-28691	NN	denotes	dehydrogenase
T16712	28669-28677	NN	denotes	pyruvate
T16711	28692-28699	NN	denotes	complex
T16710	28665-28668	DT	denotes	the
T16709	28662-28664	IN	denotes	of
T16708	28644-28653	JJ	denotes	analogous
T16707	28654-28661	NN	denotes	subunit
T16706	28641-28643	DT	denotes	an
T16705	28638-28640	IN	denotes	of
T16704	28621-28628	NN	denotes	carboxy
T16703	28629-28637	NN	denotes	terminus
T16702	28617-28620	DT	denotes	the
T16701	28700-28702	VBZ	denotes	is
T16700	28612-28616	IN	denotes	that
T16699	28598-28602	VBP	denotes	have
T16698	28603-28611	VBN	denotes	revealed
T16697	28592-28597	WDT	denotes	which
T16696	28584-28591	NNS	denotes	studies
T16695	28575-28583	JJ	denotes	previous
T16694	28570-28574	IN	denotes	with
T16693	28559-28569	JJ	denotes	consistent
T16692	28556-28558	VBZ	denotes	is
T16691	28541-28555	NN	denotes	interpretation
T16690	28536-28540	DT	denotes	This
T16689	28535-28873	sentence	denotes	This interpretation is consistent with previous studies which have revealed that the carboxy terminus of an analogous subunit of the pyruvate dehydrogenase complex is essential for subunit interactions [35] and insertion of a Hisx6 tag on the carboxy terminus of an analogous E. coli subunit interfered with normal subunit assembly [36].
T16688	28534-28535	.	denotes	.
T16687	28526-28534	NN	denotes	activity
T16686	28516-28525	JJ	denotes	enzymatic
T16685	28511-28515	IN	denotes	with
T16684	28491-28496	JJ	denotes	human
T16683	28483-28490	VBN	denotes	derived
T16682	28473-28482	NN	denotes	transgene
T16681	28497-28499	NN	denotes	E2
T16680	28469-28472	DT	denotes	the
T16679	28466-28468	IN	denotes	of
T16678	28449-28456	NN	denotes	carboxy
T16677	28457-28465	NN	denotes	terminus
T16676	28445-28448	DT	denotes	the
T16675	28442-28444	IN	denotes	at
T16674	28433-28434	HYPH	denotes	-
T16673	28434-28437	NN	denotes	myc
T16672	28432-28433	NN	denotes	c
T16671	28438-28441	NN	denotes	tag
T16670	28428-28431	DT	denotes	the
T16669	28500-28510	VBD	denotes	interfered
T16668	28423-28427	IN	denotes	that
T16667	28414-28422	JJ	denotes	probable
T16666	28411-28413	VBZ	denotes	is
T16665	28408-28410	PRP	denotes	It
T16664	28407-28535	sentence	denotes	It is probable that the c-myc tag at the carboxy terminus of the transgene derived human E2 interfered with enzymatic activity.
T16663	28406-28407	.	denotes	.
T16662	28390-28400	JJ	denotes	suboptimal
T16661	28401-28406	NN	denotes	level
T16660	28388-28389	DT	denotes	a
T16659	28385-28387	IN	denotes	at
T16658	28370-28372	VBZ	denotes	is
T16657	28359-28366	VBN	denotes	derived
T16656	28367-28369	NN	denotes	E2
T16655	28349-28358	NN	denotes	transgene
T16654	28373-28384	VBG	denotes	functioning
T16653	28344-28348	IN	denotes	that
T16652	28320-28326	NN	denotes	enzyme
T16651	28314-28319	NN	denotes	BCKDH
T16650	28327-28335	NN	denotes	activity
T16649	28307-28313	JJ	denotes	normal
T16648	28304-28306	IN	denotes	of
T16647	28302-28303	NN	denotes	%
T16646	28300-28301	SYM	denotes	–
T16645	28299-28300	CD	denotes	5
T16644	28298-28299	SYM	denotes	~
T16643	28301-28302	CD	denotes	6
T16642	28293-28297	RB	denotes	only
T16641	28290-28292	IN	denotes	in
T16640	28275-28282	NN	denotes	protein
T16639	28272-28274	NN	denotes	E2
T16638	28269-28271	IN	denotes	of
T16637	28254-28260	JJ	denotes	normal
T16636	28249-28253	RB	denotes	near
T16635	28261-28268	NNS	denotes	amounts
T16634	28243-28248	DT	denotes	these
T16633	28283-28289	VBP	denotes	result
T16632	28238-28242	IN	denotes	that
T16631	28336-28343	VBP	denotes	suggest
T16630	28225-28237	NNS	denotes	observations
T16629	28221-28224	DT	denotes	The
T16628	28220-28407	sentence	denotes	The observations that these near normal amounts of E2 protein result in only ~5–6% of normal BCKDH enzyme activity suggest that transgene derived E2 is functioning at a suboptimal level.
T16627	28219-28220	.	denotes	.
T16626	28207-28214	NN	denotes	control
T16625	28215-28219	NNS	denotes	mice
T16624	28193-28206	JJ	denotes	nontransgenic
T16623	28190-28192	IN	denotes	of
T16622	28184-28189	NN	denotes	liver
T16621	28181-28183	IN	denotes	in
T16620	28172-28180	VBN	denotes	produced
T16619	28170-28171	-RRB-	denotes	)
T16618	28165-28167	CD	denotes	47
T16617	28164-28165	SYM	denotes	~
T16616	28168-28170	NN	denotes	Kd
T16615	28163-28164	-LRB-	denotes	(
T16614	28160-28162	NN	denotes	E2
T16613	28154-28159	NN	denotes	mouse
T16612	28151-28153	IN	denotes	of
T16611	28144-28150	NN	denotes	amount
T16610	28140-28143	DT	denotes	the
T16529	27773-27776	VBD	denotes	was
T16528	27768-27772	NN	denotes	525A
T16527	27764-27767	CC	denotes	and
T16526	27762-27763	NN	denotes	A
T16525	27756-27761	NNS	denotes	Lines
T16524	27753-27755	IN	denotes	of
T16523	27747-27752	NN	denotes	liver
T16522	27744-27746	IN	denotes	in
T16521	27733-27735	NN	denotes	E2
T16520	27736-27743	NN	denotes	protein
T16519	27727-27732	JJ	denotes	human
T16518	27724-27726	IN	denotes	of
T16517	27713-27723	NN	denotes	production
T16516	27709-27712	CC	denotes	and
T16515	27693-27699	NN	denotes	enzyme
T16514	27700-27708	NN	denotes	activity
T16513	27687-27692	NN	denotes	BCKDH
T16512	27685-27687	,	denotes	,
T16511	27684-27685	-RRB-	denotes	]
T16510	27682-27684	CD	denotes	34
T16509	27681-27682	-LRB-	denotes	[
T16508	27670-27680	NN	denotes	expression
T16507	27661-27669	JJ	denotes	specific
T16506	27655-27660	NN	denotes	liver
T16505	27647-27654	VB	denotes	produce
T16504	27644-27646	TO	denotes	to
T16503	27777-27785	VBN	denotes	examined
T16502	27626-27630	VBN	denotes	been
T16482	26891-26892	sentence	denotes
T16481	26890-26891	.	denotes	.
T16480	26889-26890	-RRB-	denotes	)
T16479	26888-26889	CD	denotes	2
T16478	26882-26887	NN	denotes	Table
T16477	26881-26882	-LRB-	denotes	(
T16476	26872-26880	NNS	denotes	controls
T16475	26869-26871	IN	denotes	to
T16474	26860-26868	VBN	denotes	compared
T16473	26858-26860	,	denotes	,
T17014	30144-30148	RB	denotes	very
T17013	30156-30161	NN	denotes	model
T17012	30142-30143	DT	denotes	a
T17011	30120-30126	NN	denotes	rescue
T17010	30127-30131	NNS	denotes	mice
T17009	30114-30119	DT	denotes	these
T17008	30112-30114	,	denotes	,
T17007	30132-30141	VBP	denotes	represent
T17006	30108-30112	RB	denotes	Thus
T17005	30107-30197	sentence	denotes	Thus, these rescue mice represent a very useful model of the intermediate MSUD phenotype.
T17004	30106-30107	.	denotes	.
T17003	30105-30106	-RRB-	denotes	]
T17002	30104-30105	CD	denotes	1
T17001	30103-30104	-LRB-	denotes	[
T17000	30095-30102	NN	denotes	disease
T16999	30091-30094	DT	denotes	the
T16998	30088-30090	IN	denotes	of
T16997	30070-30082	JJ	denotes	intermediate
T16996	30083-30087	NN	denotes	form
T16995	30066-30069	DT	denotes	the
T16994	30061-30065	IN	denotes	with
T16993	30052-30060	NNS	denotes	patients
T16992	30047-30051	NN	denotes	MSUD
T16991	30044-30046	IN	denotes	in
T16990	30035-30043	VBN	denotes	observed
T16989	30016-30024	JJ	denotes	clinical
T16988	30025-30034	NN	denotes	phenotype
T16987	30012-30015	DT	denotes	the
T16986	30009-30011	IN	denotes	to
T16985	30001-30008	JJ	denotes	similar
T16984	29990-30000	RB	denotes	remarkably
T16983	29986-29989	VBP	denotes	are
T16982	29962-29972	JJ	denotes	phenotypic
T16981	29973-29985	NNS	denotes	observations
T16980	29956-29961	DT	denotes	These
T16979	29955-30107	sentence	denotes	These phenotypic observations are remarkably similar to the clinical phenotype observed in MSUD patients with the intermediate form of the disease [1].
T16978	29954-29955	.	denotes	.
T16977	29949-29954	NN	denotes	liver
T16976	29945-29948	DT	denotes	the
T16975	29942-29944	IN	denotes	in
T16974	29926-29932	NN	denotes	enzyme
T16973	29920-29925	NN	denotes	BCKDH
T16972	29933-29941	NN	denotes	activity
T16971	29913-29919	JJ	denotes	normal
T16970	29910-29912	IN	denotes	of
T16969	29908-29909	NN	denotes	%
T16968	29906-29907	SYM	denotes	–
T16967	29905-29906	CD	denotes	5
T16966	29907-29908	CD	denotes	6
T16965	29904-29905	SYM	denotes	~
T16964	29894-29903	VBD	denotes	expressed
T16963	29889-29893	PRP	denotes	they
T16962	29885-29888	CC	denotes	and
T16961	29875-29884	NNS	denotes	knockouts
T16960	29871-29874	CC	denotes	and
T16959	29862-29870	NNS	denotes	controls
T16958	29854-29861	IN	denotes	between
T16957	29841-29853	JJ	denotes	intermediate
T16956	29836-29840	VBD	denotes	were
T16955	29831-29835	WDT	denotes	that
T16954	29824-29830	NNS	denotes	ratios
T16953	29815-29816	HYPH	denotes	/
T16952	29816-29823	NN	denotes	alanine
T16951	29811-29815	NN	denotes	BCAA
T16950	29792-29801	VBG	denotes	surviving
T16949	29802-29806	NNS	denotes	mice
T16948	29786-29791	DT	denotes	these
T16947	29784-29786	,	denotes	,
T16946	29777-29784	NN	denotes	summary
T16945	29807-29810	VBD	denotes	had
T16944	29774-29776	IN	denotes	In
T16943	29773-29955	sentence	denotes	In summary, these surviving mice had BCAA/alanine ratios that were intermediate between controls and knockouts and they expressed ~5–6% of normal BCKDH enzyme activity in the liver.
T16942	29772-29773	.	denotes	.
T16941	29769-29772	NN	denotes	age
T16940	29766-29768	IN	denotes	of
T16939	29757-29759	CD	denotes	60
T16938	29753-29756	CC	denotes	and
T16937	29760-29765	NNS	denotes	weeks
T16936	29750-29752	CD	denotes	40
T16935	29747-29749	IN	denotes	at
T16934	29742-29746	VBD	denotes	died
T16933	29727-29731	JJ	denotes	rare
T16932	29723-29726	CD	denotes	two
T16931	29732-29741	NNS	denotes	survivors
T16930	29717-29722	DT	denotes	These
T16929	29716-29773	sentence	denotes	These two rare survivors died at 40 and 60 weeks of age.
T16928	29715-29716	.	denotes	.
T16927	29710-29715	JJ	denotes	alive
T16926	29704-29709	RB	denotes	still
T16925	29697-29698	-RRB-	denotes	)
T16924	29695-29697	CD	denotes	16
T16923	29692-29694	IN	denotes	of
T16922	29690-29691	CD	denotes	2
T16921	29689-29690	-LRB-	denotes	(
T16920	29684-29688	NNS	denotes	mice
T16919	29681-29683	IN	denotes	of
T16918	29679-29680	NN	denotes	%
T16917	29677-29679	CD	denotes	12
T16916	29676-29677	SYM	denotes	~
T16915	29674-29676	,	denotes	,
T16914	29671-29674	NN	denotes	age
T16913	29668-29670	IN	denotes	of
T16912	29662-29667	NNS	denotes	weeks
T16911	29659-29661	CD	denotes	20
T16910	29699-29703	VBD	denotes	were
T16909	29656-29658	IN	denotes	At
T16908	29655-29716	sentence	denotes	At 20 weeks of age, ~12% of mice (2 of 16) were still alive.
T16907	29654-29655	.	denotes	.
T16906	29648-29654	JJR	denotes	better
T16905	29639-29647	RB	denotes	somewhat
T16904	29636-29638	VB	denotes	be
T16903	29633-29635	TO	denotes	to
T16902	29619-29623	NN	denotes	525A
T16901	29614-29618	NN	denotes	Line
T16900	29611-29613	IN	denotes	of
T16899	29624-29632	VBD	denotes	appeared
T16898	29602-29610	NN	denotes	Survival
T16897	29601-29655	sentence	denotes	Survival of Line 525A appeared to be somewhat better.
T16896	29600-29601	.	denotes	.
T16895	29596-29600	NN	denotes	cage
T16894	29590-29595	PRP$	denotes	their
T16893	29587-29589	IN	denotes	in
T16892	29582-29586	JJ	denotes	dead
T16891	29576-29581	VBN	denotes	found
T16890	29571-29575	VBD	denotes	were
T16889	29568-29570	CC	denotes	or
T16888	29566-29568	,	denotes	,
T16887	29556-29566	VBN	denotes	sacrificed
T16886	29547-29555	RB	denotes	humanely
T16885	29543-29546	CC	denotes	and
T16884	29534-29542	JJ	denotes	moribund
T16883	29527-29528	NN	denotes	A
T16882	29522-29526	NN	denotes	Line
T16881	29519-29521	IN	denotes	of
T16880	29514-29518	NNS	denotes	mice
T16879	29510-29513	DT	denotes	all
T16878	29508-29510	,	denotes	,
T16877	29503-29508	NNS	denotes	weeks
T16876	29500-29502	CD	denotes	16
T16875	29529-29533	VBD	denotes	were
T16874	29497-29499	IN	denotes	By
T16873	29496-29601	sentence	denotes	By 16 weeks, all mice of Line A were moribund and humanely sacrificed, or were found dead in their cage.
T16872	29495-29496	.	denotes	.
T16871	29480-29483	VBD	denotes	was
T16870	29468-29474	NN	denotes	rescue
T16869	29475-29479	NNS	denotes	mice
T16868	29464-29467	DT	denotes	the
T16867	29461-29463	IN	denotes	of
T16866	29452-29460	NN	denotes	survival
T16865	29484-29495	VBN	denotes	compromised
T16864	29447-29451	IN	denotes	that
T16863	29438-29446	JJ	denotes	apparent
T16862	29430-29437	RB	denotes	readily
T16861	29424-29426	PRP	denotes	it
T16860	29422-29424	,	denotes	,
T16859	29427-29429	VBZ	denotes	is
T16858	29409-29412	RB	denotes	not
T16857	29405-29408	VBD	denotes	was
T16856	29397-29404	NNS	denotes	animals
T16855	29389-29396	NN	denotes	control
T16854	29385-29388	IN	denotes	for
T16853	29380-29384	NNS	denotes	data
T16852	29371-29379	NN	denotes	survival
T16851	29413-29422	VBN	denotes	collected
T16850	29362-29370	IN	denotes	Although
T16849	29361-29496	sentence	denotes	Although survival data for control animals was not collected, it is readily apparent that survival of the rescue mice was compromised.
T16848	29360-29361	.	denotes	.
T16847	29358-29360	NN	denotes	4D
T16846	29353-29357	NN	denotes	Fig.
T16845	29350-29352	IN	denotes	in
T16844	29339-29341	VBZ	denotes	is
T16843	29331-29338	NN	denotes	weaning
T16842	29324-29330	IN	denotes	beyond
T16841	29315-29323	VBD	denotes	survived
T16840	29310-29314	WDT	denotes	that
T16839	29293-29303	JJ	denotes	transgenic
T16838	29289-29292	CD	denotes	two
T16837	29304-29309	NNS	denotes	lines
T16836	29283-29288	DT	denotes	these
T16835	29278-29282	IN	denotes	from
T16834	29273-29277	NNS	denotes	mice
T16833	29269-29272	DT	denotes	the
T16832	29266-29268	IN	denotes	of
T16831	29342-29349	VBN	denotes	plotted
T16830	29257-29265	NN	denotes	survival
T16829	29251-29252	HYPH	denotes	-
T16828	29252-29256	NN	denotes	term
T16827	29247-29251	JJ	denotes	Long
T16826	29246-29361	sentence	denotes	Long-term survival of the mice from these two transgenic lines that survived beyond weaning is plotted in Fig. 4D.
T16472	26854-26858	NNS	denotes	mice
T16471	26849-26853	NN	denotes	525A
T16470	26844-26848	NN	denotes	Line
T16469	26841-26843	IN	denotes	in
T16468	26831-26840	NN	denotes	glutamate
T16467	26827-26830	VBD	denotes	was
T16466	26824-26826	IN	denotes	as
T16465	26822-26824	,	denotes	,
T16464	26818-26822	NNS	denotes	mice
T16463	26816-26817	NN	denotes	A
T16462	26811-26815	NN	denotes	Line
T16461	26808-26810	IN	denotes	in
T16460	26795-26799	VBD	denotes	were
T16459	26785-26794	NN	denotes	glutamine
T16458	26781-26784	CC	denotes	and
T16457	26779-26781	,	denotes	,
T16456	26770-26779	NN	denotes	glutamate
T16455	26768-26770	,	denotes	,
T16454	26761-26768	NN	denotes	alanine
T16453	26758-26760	IN	denotes	of
T16452	26800-26807	VBN	denotes	reduced
T16451	26751-26757	NNS	denotes	levels
T16450	26745-26750	NN	denotes	Blood
T16449	26744-26891	sentence	denotes	Blood levels of alanine, glutamate, and glutamine were reduced in Line A mice, as was glutamate in Line 525A mice, compared to controls (Table 2).
T16448	26743-26744	.	denotes	.
T16447	26742-26743	-RRB-	denotes	)
T16446	26740-26742	NN	denotes	2C
T16445	26733-26739	NN	denotes	Figure
T16444	26729-26732	VB	denotes	see
T16443	26728-26729	-LRB-	denotes	(
T16442	26718-26727	NNS	denotes	knockouts
T16441	26714-26717	CC	denotes	and
T16440	26705-26713	NNS	denotes	controls
T16439	26697-26704	IN	denotes	between
T16438	26684-26696	JJ	denotes	intermediate
T16437	26664-26674	JJ	denotes	transgenic
T16436	26675-26679	NNS	denotes	mice
T16435	26660-26663	DT	denotes	the
T16434	26656-26659	IN	denotes	for
T16433	26640-26641	HYPH	denotes	/
T16432	26641-26648	NN	denotes	alanine
T16431	26636-26640	NN	denotes	BCAA
T16430	26649-26655	NNS	denotes	values
T16429	26632-26635	DT	denotes	the
T16428	26680-26683	VBP	denotes	are
T16427	26627-26631	IN	denotes	that
T16426	26622-26626	VB	denotes	Note
T16425	26621-26744	sentence	denotes	Note that the BCAA/alanine values for the transgenic mice are intermediate between controls and knockouts (see Figure 2C).
T16424	26620-26621	.	denotes	.
T16423	26612-26620	VBN	denotes	analyzed
T16422	26600-26604	NN	denotes	time
T16421	26605-26611	NNS	denotes	points
T16420	26596-26599	DT	denotes	the
T16419	26593-26595	IN	denotes	of
T16418	26589-26592	DT	denotes	all
T16417	26585-26588	IN	denotes	for
T16416	26576-26584	NNS	denotes	controls
T16415	26573-26575	IN	denotes	to
T16414	26564-26572	VBN	denotes	compared
T16413	26555-26563	JJ	denotes	elevated
T16412	26541-26554	RB	denotes	significantly
T16411	26530-26535	NNS	denotes	lines
T16410	26525-26529	DT	denotes	both
T16409	26520-26524	IN	denotes	from
T16408	26515-26519	NNS	denotes	mice
T16407	26511-26514	IN	denotes	for
T16406	26536-26540	VBD	denotes	were
T16405	26495-26496	HYPH	denotes	/
T16404	26496-26503	NN	denotes	alanine
T16403	26491-26495	NN	denotes	BCAA
T16402	26504-26510	NNS	denotes	values
T16401	26487-26490	DT	denotes	The
T16400	26486-26621	sentence	denotes	The BCAA/alanine values for mice from both lines were significantly elevated compared to controls for all of the time points analyzed.
T16399	26485-26486	.	denotes	.
T16398	26478-26485	NN	denotes	alanine
T16397	26475-26477	IN	denotes	to
T16396	26470-26474	NN	denotes	BCAA
T16395	26464-26469	JJ	denotes	total
T16394	26461-26463	IN	denotes	of
T16393	26455-26460	NN	denotes	ratio
T16392	26453-26454	DT	denotes	a
T16391	26450-26452	IN	denotes	as
T16390	26440-26449	VBN	denotes	presented
T16389	26426-26430	NN	denotes	acid
T16388	26420-26425	NN	denotes	amino
T16387	26431-26439	NN	denotes	analysis
T16386	26414-26419	NN	denotes	blood
T16385	26411-26413	IN	denotes	of
T16384	26403-26410	NNS	denotes	results
T16383	26399-26402	DT	denotes	the
T16337	26323-26324	sentence	denotes	L
T16336	25154-25155	sentence	denotes
T16335	25153-25154	.	denotes	.
T16334	25149-25153	NNS	denotes	pups
T16333	25142-25148	VBN	denotes	weaned
T16332	25139-25141	IN	denotes	of
T16331	25136-25137	CD	denotes	5
T16330	25132-25135	CC	denotes	and
T16329	25137-25138	NN	denotes	%
T16328	25130-25131	CD	denotes	1
T16327	25122-25129	IN	denotes	between
T16326	25112-25121	NN	denotes	frequency
T16325	25110-25111	DT	denotes	a
T16324	25107-25109	IN	denotes	at
T16323	25092-25098	NN	denotes	rescue
T16322	25099-25106	NNS	denotes	animals
T16277	24848-24849	.	denotes	.
T16276	24833-24839	NN	denotes	rescue
T16275	24840-24848	NN	denotes	genotype
T16274	24829-24832	DT	denotes	the
T16273	24820-24824	NN	denotes	line
T16272	24815-24819	DT	denotes	this
T16271	24810-24814	IN	denotes	from
T16270	24795-24804	VBG	denotes	surviving
T16269	24793-24795	,	denotes	,
T16268	24805-24809	NNS	denotes	pups
T16267	24787-24793	VBN	denotes	weaned
T16266	24784-24786	IN	denotes	of
T16265	24825-24828	VBD	denotes	had
T16264	24782-24783	NN	denotes	%
T16263	24780-24782	CD	denotes	10
T16262	24766-24779	RB	denotes	Approximately
T16261	24765-24849	sentence	denotes	Approximately 10% of weaned, surviving pups from this line had the rescue genotype.
T16260	24764-24765	.	denotes	.
T16259	24759-24762	CD	denotes	525
T16258	24763-24764	NN	denotes	A
T16257	24754-24758	NN	denotes	line
T16256	24742-24749	NN	denotes	weaning
T16255	24739-24741	IN	denotes	at
T16254	24734-24738	NNS	denotes	mice
T16253	24727-24733	NN	denotes	rescue
T16252	24724-24726	IN	denotes	of
T16251	24705-24712	JJS	denotes	highest
T16250	24713-24723	NN	denotes	percentage
T16249	24701-24704	DT	denotes	the
T16248	24696-24700	IN	denotes	with
T16247	24750-24753	VBD	denotes	was
T16246	24691-24695	NN	denotes	line
T16245	24687-24690	DT	denotes	The
T16244	24686-24765	sentence	denotes	The line with the highest percentage of rescue mice at weaning was line 525 A.
T16243	24685-24686	.	denotes	.
T16242	24680-24685	NNS	denotes	lines
T16241	24672-24679	IN	denotes	between
T16240	24659-24662	VBD	denotes	was
T16239	24663-24671	VBN	denotes	observed
T16238	24647-24658	NN	denotes	variability
T16237	24634-24646	JJ	denotes	Considerable
T16236	24633-24686	sentence	denotes	Considerable variability was observed between lines.
T16235	24632-24633	.	denotes	.
T16234	24626-24632	VBN	denotes	tested
T16233	24610-24620	JJ	denotes	transgenic
T16232	24621-24625	NN	denotes	line
T16231	24605-24609	DT	denotes	each
T16230	24600-24604	IN	denotes	from
T16229	24584-24590	NN	denotes	rescue
T16220	24539-24549	NN	denotes	percentage
T17021	30196-30197	.	denotes	.
T17020	30182-30186	NN	denotes	MSUD
T17019	30169-30181	JJ	denotes	intermediate
T17018	30187-30196	NN	denotes	phenotype
T17017	30165-30168	DT	denotes	the
T17016	30162-30164	IN	denotes	of
T16609	28137-28139	IN	denotes	to
T16608	28131-28136	JJ	denotes	equal
T16607	28117-28130	RB	denotes	approximately
T16606	28110-28112	NN	denotes	E2
T16605	28104-28109	JJ	denotes	human
T16604	28101-28103	IN	denotes	of
T16603	28095-28100	NN	denotes	level
T16602	28091-28094	DT	denotes	the
T16601	28089-28091	,	denotes	,
T16600	28074-28084	JJ	denotes	transgenic
T16599	28085-28089	NNS	denotes	mice
T16598	28068-28073	DT	denotes	these
T16597	28065-28067	IN	denotes	of
T16596	28060-28064	DT	denotes	some
T16595	28113-28116	VBD	denotes	was
T16594	28057-28059	IN	denotes	In
T16593	28056-28220	sentence	denotes	In some of these transgenic mice, the level of human E2 was approximately equal to the amount of mouse E2 (~47 Kd) produced in liver of nontransgenic control mice.
T16592	28055-28056	.	denotes	.
T16591	28051-28055	NNS	denotes	mice
T16590	28043-28050	IN	denotes	between
T16589	28034-28042	JJ	denotes	variable
T16588	28028-28033	RB	denotes	quite
T16587	28008-28018	JJ	denotes	transgenic
T16586	28019-28023	NNS	denotes	mice
T16585	28002-28007	DT	denotes	these
T16584	27999-28001	IN	denotes	in
T16583	27997-27998	-RRB-	denotes	)
T16582	27992-27994	NN	denotes	54
T16581	27991-27992	SYM	denotes	~
T16580	27989-27991	NN	denotes	MW
T16579	27979-27988	VBN	denotes	predicted
T16578	27995-27997	NN	denotes	Kd
T16577	27978-27979	-LRB-	denotes	(
T16576	27975-27977	NN	denotes	E2
T16575	27969-27974	JJ	denotes	human
T16574	27966-27968	IN	denotes	of
T16573	27959-27965	NN	denotes	amount
T16572	27955-27958	DT	denotes	the
T16571	27953-27955	,	denotes	,
T16570	27951-27953	NN	denotes	3B
T16569	27946-27950	NNP	denotes	Fig.
T16568	27943-27945	IN	denotes	in
T16567	28024-28027	VBD	denotes	was
T16566	27937-27942	VBN	denotes	shown
T16565	27934-27936	IN	denotes	As
T16564	27933-28056	sentence	denotes	As shown in Fig. 3B, the amount of human E2 (predicted MW~54 Kd) in these transgenic mice was quite variable between mice.
T16563	27932-27933	.	denotes	.
T16562	27931-27932	-RRB-	denotes	)
T16561	27924-27928	NN	denotes	Fig.
T16560	27929-27931	NN	denotes	4C
T16559	27923-27924	-LRB-	denotes	(
T16558	27917-27922	NN	denotes	liver
T16557	27909-27916	NN	denotes	control
T16556	27906-27908	IN	denotes	in
T16555	27898-27905	JJ	denotes	present
T16554	27879-27888	JJ	denotes	enzymatic
T16553	27889-27897	NN	denotes	activity
T16552	27875-27878	DT	denotes	the
T16551	27872-27874	IN	denotes	of
T16550	27870-27872	,	denotes	,
T16549	27858-27870	RB	denotes	respectively
T16548	27856-27858	,	denotes	,
T16547	27854-27855	CD	denotes	5
T16546	27850-27853	CC	denotes	and
T16545	27855-27856	NN	denotes	%
T16544	27848-27849	CD	denotes	6
T16543	27847-27848	SYM	denotes	~
T16542	27838-27842	NN	denotes	525A
T16541	27834-27837	CC	denotes	and
T16540	27832-27833	NN	denotes	A
T16539	27826-27831	NNS	denotes	Lines
T16538	27821-27825	IN	denotes	from
T16537	27815-27820	NN	denotes	liver
T16536	27812-27814	IN	denotes	in
T16535	27843-27846	VBD	denotes	was
T16534	27793-27802	JJ	denotes	enzymatic
T16533	27803-27811	NN	denotes	activity
T16532	27787-27792	NN	denotes	BCKDH
T16531	27786-27933	sentence	denotes	BCKDH enzymatic activity in liver from Lines A and 525A was ~6 and 5%, respectively, of the enzymatic activity present in control liver (Fig. 4C).
T16530	27785-27786	.	denotes	.
T16228	24591-24599	NN	denotes	genotype
T16227	24580-24583	DT	denotes	the
T16226	24575-24579	IN	denotes	with
T16225	24567-24574	NN	denotes	weaning
T16224	24564-24566	IN	denotes	at
T16223	24558-24563	JJ	denotes	alive
T16222	24553-24557	NNS	denotes	mice
T16221	24550-24552	IN	denotes	of
T16219	24535-24538	DT	denotes	the
T16218	24529-24534	VBZ	denotes	shows
T16217	24526-24528	NN	denotes	4A
T16216	24521-24525	NN	denotes	Fig.
T16215	24520-24633	sentence	denotes	Fig. 4A shows the percentage of mice alive at weaning with the rescue genotype from each transgenic line tested.
T16214	24519-24520	.	denotes	.
T16213	24518-24519	NN	denotes	%
T16212	24516-24518	CD	denotes	14
T16211	24513-24515	IN	denotes	of
T16210	24511-24512	-RRB-	denotes	)
T16209	24501-24511	NNS	denotes	transgenes
T16208	24496-24500	DT	denotes	both
T16207	24492-24495	IN	denotes	for
T16206	24483-24491	JJ	denotes	positive
T16205	24479-24482	CC	denotes	and
T16204	24467-24469	NN	denotes	E2
T16203	24456-24466	JJ	denotes	homozygous
T16202	24454-24456	,	denotes	,
T16201	24450-24454	FW	denotes	i.e.
T16200	24470-24478	NN	denotes	knockout
T16199	24449-24450	-LRB-	denotes	(
T16198	24433-24439	NN	denotes	rescue
T16197	24440-24448	NN	denotes	genotype
T16196	24429-24432	DT	denotes	the
T16195	24424-24428	IN	denotes	with
T16194	24416-24423	NNS	denotes	animals
T16193	24413-24415	IN	denotes	of
T16192	24393-24404	JJ	denotes	theoretical
T16191	24405-24412	NN	denotes	maximum
T16190	24391-24392	DT	denotes	a
T16189	24388-24390	IN	denotes	in
T16188	24381-24387	VB	denotes	result
T16187	24378-24380	TO	denotes	to
T16186	24366-24368	VBZ	denotes	is
T16185	24369-24377	VBN	denotes	expected
T16184	24348-24356	VBG	denotes	breeding
T16183	24357-24365	NN	denotes	strategy
T16182	24343-24347	DT	denotes	This
T16181	24342-24520	sentence	denotes	This breeding strategy is expected to result in a theoretical maximum of animals with the rescue genotype (i.e., homozygous E2 knockout and positive for both transgenes) of 14%.
T16180	24341-24342	.	denotes	.
T16179	24334-24341	NN	denotes	weaning
T16178	24331-24333	IN	denotes	at
T16177	24323-24330	NNS	denotes	litters
T16176	24310-24312	PRP	denotes	we
T16175	24308-24310	,	denotes	,
T16174	24299-24308	NN	denotes	lethality
T16173	24290-24298	JJ	denotes	neonatal
T16172	24285-24289	IN	denotes	from
T16171	24276-24284	NN	denotes	knockout
T16170	24272-24275	DT	denotes	the
T16169	24265-24271	VB	denotes	rescue
T16168	24262-24264	TO	denotes	to
T16167	24251-24261	NNS	denotes	transgenes
T16166	24247-24250	DT	denotes	the
T16165	24244-24246	IN	denotes	of
T16164	24236-24243	NN	denotes	ability
T16163	24232-24235	DT	denotes	the
T16162	24228-24231	IN	denotes	for
T16161	24313-24322	VBD	denotes	genotyped
T16160	24209-24220	RB	denotes	efficiently
T16159	24221-24227	VB	denotes	screen
T16158	24206-24208	TO	denotes	To
T16157	24205-24342	sentence	denotes	To efficiently screen for the ability of the transgenes to rescue the knockout from neonatal lethality, we genotyped litters at weaning.
T16156	24204-24205	.	denotes	.
T16155	24193-24195	NN	denotes	E2
T16154	24196-24204	NN	denotes	knockout
T16153	24189-24192	DT	denotes	the
T16152	24185-24188	CC	denotes	and
T16151	24183-24185	,	denotes	,
T16150	24170-24171	HYPH	denotes	-
T16149	24171-24173	NN	denotes	E2
T16148	24167-24170	NN	denotes	TRE
T16147	24174-24183	NN	denotes	transgene
T16146	24163-24166	DT	denotes	the
T16145	24161-24163	,	denotes	,
T16144	24147-24148	HYPH	denotes	-
T16143	24148-24151	NN	denotes	tTA
T16142	24144-24147	NN	denotes	LAP
T16141	24152-24161	NN	denotes	transgene
T16140	24140-24143	DT	denotes	the
T16139	24136-24139	IN	denotes	for
T16138	24123-24135	JJ	denotes	heterozygous
T16137	24113-24117	NNS	denotes	mice
T16136	24109-24112	DT	denotes	the
T16135	24103-24108	WDT	denotes	which
T16134	24118-24122	VBD	denotes	were
T16133	24100-24102	IN	denotes	in
T16132	24090-24094	VBD	denotes	were
T16131	24084-24089	NNS	denotes	pairs
T16130	24075-24083	VBG	denotes	breeding
T16129	24073-24075	,	denotes	,
T16128	24095-24099	VBN	denotes	used
T16127	24063-24073	RB	denotes	Ultimately
T16126	24062-24205	sentence	denotes	Ultimately, breeding pairs were used in which the mice were heterozygous for the LAP-tTA transgene, the TRE-E2 transgene, and the E2 knockout.
T16125	24061-24062	.	denotes	.
T16124	24050-24052	NN	denotes	E2
T16123	24053-24061	NN	denotes	knockout
T16122	24046-24049	DT	denotes	the
T16121	24042-24045	IN	denotes	for
T16120	24029-24041	JJ	denotes	heterozygous
T16119	24024-24028	VBD	denotes	were
T16118	24020-24023	CC	denotes	and
T16117	24005-24006	HYPH	denotes	-
T16116	24006-24009	NN	denotes	tTA
T16115	24002-24005	NN	denotes	LAP
T16114	24010-24019	NN	denotes	transgene
T16113	23998-24001	DT	denotes	the
T16112	23994-23997	IN	denotes	for
T16111	23985-23993	JJ	denotes	positive
T16110	23980-23984	VBD	denotes	were
T16109	23975-23979	WDT	denotes	that
T16108	23970-23974	NNS	denotes	mice
T16107	23967-23969	IN	denotes	to
T16106	23954-23958	VBD	denotes	were
T16105	23952-23953	-RRB-	denotes	)
T16104	23940-23942	NN	denotes	F1
T16103	23937-23939	CC	denotes	or
T16102	23928-23936	NNS	denotes	founders
T16101	23921-23927	CC	denotes	either
T16100	23943-23952	NN	denotes	offspring
T16099	23920-23921	-LRB-	denotes	(
T16098	23915-23919	NN	denotes	line
T16097	23910-23914	DT	denotes	each
T16096	23905-23909	IN	denotes	from
T16095	23959-23966	VBN	denotes	crossed
T16094	23896-23897	HYPH	denotes	-
T16093	23897-23899	NN	denotes	E2
T16092	23893-23896	NN	denotes	TRE
T16091	23900-23904	NNS	denotes	mice
T16090	23882-23892	JJ	denotes	Transgenic
T16089	23881-24062	sentence	denotes	Transgenic TRE-E2 mice from each line (either founders or F1 offspring) were crossed to mice that were positive for the LAP-tTA transgene and were heterozygous for the E2 knockout.
T16088	23880-23881	.	denotes	.
T16087	23879-23880	-RRB-	denotes	)
T16086	23870-23873	RB	denotes	not
T16085	23865-23869	NNS	denotes	data
T16084	23874-23879	VBN	denotes	shown
T16083	23864-23865	-LRB-	denotes	(
T16082	23860-23863	NN	denotes	DNA
T16081	23855-23859	NN	denotes	tail
T16080	23852-23854	IN	denotes	of
T16079	23843-23851	NN	denotes	analysis
T16078	23838-23842	NN	denotes	blot
T16077	23829-23837	NNP	denotes	Southern
T16076	23826-23828	IN	denotes	by
T16075	23817-23825	VBN	denotes	compared
T16074	23814-23816	IN	denotes	as
T16073	23802-23806	NN	denotes	copy
T16072	23807-23813	NN	denotes	number
T16071	23792-23801	NN	denotes	transgene
T16070	23789-23791	IN	denotes	in
T15888	21692-21699	JJ	denotes	minimal
T15887	21681-21691	VBG	denotes	containing
T15886	21677-21680	NN	denotes	TRE
T15885	21675-21676	DT	denotes	a
T15884	21670-21674	IN	denotes	from
T15883	21662-21664	NN	denotes	E2
T15882	21656-21661	JJ	denotes	human
T15881	21665-21669	NN	denotes	cDNA
T15880	21654-21655	DT	denotes	a
T15879	21646-21653	VB	denotes	express
T15878	21643-21645	TO	denotes	to
T15877	21630-21633	VBD	denotes	was
T15876	21634-21642	VBN	denotes	designed
T15875	21616-21617	HYPH	denotes	-
T15874	21617-21619	NN	denotes	E2
T15873	21613-21616	NN	denotes	TRE
T15872	21620-21629	NN	denotes	transgene
T15871	21609-21612	DT	denotes	The
T15870	21608-21733	sentence	denotes	The TRE-E2 transgene was designed to express a human E2 cDNA from a TRE containing minimal promoter upon stimulation by tTA.
T15869	21607-21608	.	denotes	.
T15868	21606-21607	-RRB-	denotes	)
T15867	21603-21606	NN	denotes	TRE
T15866	21602-21603	-LRB-	denotes	(
T15865	21585-21593	NN	denotes	response
T15864	21570-21584	NN	denotes	transactivator
T15863	21594-21601	NN	denotes	element
T15862	21568-21569	DT	denotes	a
T15861	21561-21567	VBP	denotes	harbor
T15860	21556-21560	WDT	denotes	that
T15859	21546-21555	NNS	denotes	promoters
T15858	21543-21545	IN	denotes	of
T15857	21532-21542	NN	denotes	expression
T15856	21521-21531	VBZ	denotes	stimulates
T15855	21516-21520	WDT	denotes	that
T15854	21495-21508	NN	denotes	transcription
T15853	21509-21515	NN	denotes	factor
T15852	21493-21494	DT	denotes	a
T15851	21491-21493	,	denotes	,
T15850	21490-21491	-RRB-	denotes	)
T15849	21487-21490	NN	denotes	tTA
T15848	21486-21487	-LRB-	denotes	(
T15847	21459-21460	HYPH	denotes	-
T15846	21460-21470	VBN	denotes	controlled
T15845	21447-21459	NN	denotes	tetracycline
T15844	21471-21485	NN	denotes	transactivator
T15843	21443-21446	DT	denotes	the
T15842	21440-21442	IN	denotes	of
T15841	21429-21439	NN	denotes	expression
T15840	21420-21428	JJ	denotes	specific
T15839	21414-21419	NN	denotes	liver
T15838	21411-21413	IN	denotes	of
T15837	21404-21410	NNS	denotes	levels
T15836	21399-21403	JJ	denotes	high
T15835	21389-21390	-RRB-	denotes	]
T15834	21387-21389	CD	denotes	34
T15833	21386-21387	-LRB-	denotes	[
T15832	21391-21398	VBZ	denotes	directs
T15831	21371-21372	HYPH	denotes	-
T15830	21372-21375	NN	denotes	tTA
T15829	21368-21371	NN	denotes	LAP
T15828	21376-21385	NN	denotes	transgene
T15827	21364-21367	DT	denotes	The
T15826	21363-21608	sentence	denotes	The LAP-tTA transgene [34] directs high levels of liver specific expression of the tetracycline-controlled transactivator (tTA), a transcription factor that stimulates expression of promoters that harbor a transactivator response element (TRE).
T15825	21362-21363	.	denotes	.
T15824	21361-21362	-RRB-	denotes	)
T15823	21354-21358	NN	denotes	Fig.
T15822	21359-21361	NN	denotes	3A
T15821	21353-21354	-LRB-	denotes	(
T15820	21339-21340	HYPH	denotes	-
T15819	21340-21342	NN	denotes	E2
T15818	21336-21339	NN	denotes	TRE
T15817	21343-21352	NN	denotes	transgene
T15816	21334-21335	DT	denotes	a
T15815	21330-21333	CC	denotes	and
T15814	21315-21316	HYPH	denotes	-
T15813	21316-21319	NN	denotes	tTA
T15812	21312-21315	NN	denotes	LAP
T15811	21320-21329	NN	denotes	transgene
T15810	21310-21311	DT	denotes	a
T15809	21307-21309	IN	denotes	of
T15808	21297-21306	VBD	denotes	consisted
T15807	21276-21289	JJ	denotes	bi-transgenic
T15806	21290-21296	NN	denotes	system
T15805	21271-21275	DT	denotes	This
T15804	21270-21363	sentence	denotes	This bi-transgenic system consisted of a LAP-tTA transgene and a TRE-E2 transgene (Fig. 3A).
T15803	21269-21270	.	denotes	.
T15802	21250-21258	NN	denotes	knockout
T15801	21247-21249	NN	denotes	E2
T15800	21259-21269	NN	denotes	background
T15799	21243-21246	DT	denotes	the
T15798	21240-21242	IN	denotes	on
T15797	21234-21239	NN	denotes	liver
T15796	21231-21233	IN	denotes	in
T15795	21228-21230	NN	denotes	E2
T15794	21222-21227	JJ	denotes	human
T15793	21214-21221	VB	denotes	express
T15792	21211-21213	TO	denotes	to
T15791	21193-21203	JJ	denotes	transgenic
T15790	21188-21192	NN	denotes	part
T15789	21184-21187	CD	denotes	two
T15788	21204-21210	NN	denotes	system
T15787	21182-21183	DT	denotes	a
T15786	21179-21181	IN	denotes	of
T15785	21166-21169	VBD	denotes	was
T15784	21170-21178	VBN	denotes	composed
T15783	21157-21165	NN	denotes	strategy
T15782	21153-21156	PRP$	denotes	Our
T15781	21152-21270	sentence	denotes	Our strategy was composed of a two part transgenic system to express human E2 in liver on the E2 knockout background.
T15780	21151-21152	.	denotes	.
T15779	21140-21145	NN	denotes	mouse
T15778	21135-21139	NN	denotes	MSUD
T15777	21127-21134	JJ	denotes	classic
T15776	21146-21151	NN	denotes	model
T15775	21123-21126	DT	denotes	the
T15774	21120-21122	IN	denotes	in
T15773	21113-21119	VBZ	denotes	occurs
T15772	21108-21112	WDT	denotes	that
T15771	21098-21107	NN	denotes	lethality
T15770	21089-21097	JJ	denotes	neonatal
T15769	21085-21088	CC	denotes	and
T15768	21080-21084	NN	denotes	BCAA
T15767	21077-21079	IN	denotes	of
T15766	21060-21066	JJ	denotes	severe
T15765	21067-21076	NN	denotes	elevation
T15764	21056-21059	DT	denotes	the
T15763	21049-21055	VB	denotes	rescue
T15762	21046-21048	TO	denotes	to
T15761	21026-21036	JJ	denotes	transgenic
T15760	21037-21045	NN	denotes	strategy
T15759	21024-21025	DT	denotes	a
T15758	21016-21018	PRP	denotes	we
T15757	21014-21016	,	denotes	,
T15756	21010-21014	NN	denotes	MSUD
T15755	21007-21009	IN	denotes	of
T15754	20994-21001	NN	denotes	variant
T15753	20981-20993	JJ	denotes	intermediate
T15752	21002-21006	NN	denotes	form
T15751	20977-20980	DT	denotes	the
T15750	20974-20976	IN	denotes	of
T15749	20961-20967	JJ	denotes	murine
T15748	20968-20973	NN	denotes	model
T15747	20959-20960	DT	denotes	a
T15746	21019-21023	VBD	denotes	used
T15745	20952-20958	VB	denotes	create
T15744	20949-20951	TO	denotes	To
T15743	20948-21152	sentence	denotes	To create a murine model of the intermediate variant form of MSUD, we used a transgenic strategy to rescue the severe elevation of BCAA and neonatal lethality that occurs in the classic MSUD mouse model.
T15742	20944-20948	NN	denotes	MSUD
T15741	20931-20943	JJ	denotes	intermediate
T15740	20924-20930	VBZ	denotes	mimics
T15739	20919-20923	WDT	denotes	that
T15738	20914-20918	NN	denotes	MSUD
T15737	20911-20913	IN	denotes	of
T15736	20898-20905	JJ	denotes	variant
T15735	20906-20910	NN	denotes	form
T15734	20896-20897	DT	denotes	a
T15733	20877-20879	NN	denotes	E2
T15732	20871-20876	JJ	denotes	human
T15731	20880-20889	NN	denotes	transgene
T15730	20869-20870	DT	denotes	a
T15729	20858-20868	VBG	denotes	expressing
T15728	20890-20895	VBP	denotes	model
T15727	20853-20857	NNS	denotes	mice
T15726	20844-20852	NN	denotes	Knockout
T16069	23775-23788	RB	denotes	substantially
T16068	23766-23774	VBD	denotes	differed
T16067	23760-23765	NNS	denotes	lines
T16066	23754-23759	DT	denotes	These
T16065	23753-23881	sentence	denotes	These lines differed substantially in transgene copy number as compared by Southern blot analysis of tail DNA (data not shown).
T16064	23752-23753	.	denotes	.
T16063	23747-23752	NNS	denotes	lines
T16062	23741-23746	DT	denotes	these
T16061	23738-23740	IN	denotes	of
T16060	23736-23737	CD	denotes	9
T16059	23733-23735	IN	denotes	of
T16058	23727-23732	NN	denotes	total
T16057	23725-23726	DT	denotes	a
T16056	23722-23724	IN	denotes	on
T16055	23711-23715	RB	denotes	only
T16054	23708-23710	TO	denotes	to
T16053	23716-23721	VB	denotes	focus
T16052	23705-23707	PRP	denotes	us
T16051	23697-23704	VBD	denotes	allowed
T16050	23687-23696	NNS	denotes	resources
T16049	23679-23686	VBN	denotes	Limited
T16048	23678-23753	sentence	denotes	Limited resources allowed us to only focus on a total of 9 of these lines.
T16047	23677-23678	.	denotes	.
T16046	23669-23677	NNS	denotes	founders
T16045	23663-23668	DT	denotes	these
T16044	23658-23662	IN	denotes	from
T16043	23641-23651	JJ	denotes	transgenic
T16042	23631-23640	JJ	denotes	different
T16041	23652-23657	NNS	denotes	lines
T16040	23628-23630	CD	denotes	15
T16039	23625-23627	IN	denotes	of
T16038	23619-23624	NN	denotes	total
T16037	23617-23618	DT	denotes	a
T16036	23605-23616	VBD	denotes	established
T16035	23602-23604	PRP	denotes	We
T16034	23601-23678	sentence	denotes	We established a total of 15 different transgenic lines from these founders.
T16033	23600-23601	.	denotes	.
T16032	23590-23600	VBD	denotes	segregated
T16031	23585-23589	WDT	denotes	that
T16030	23569-23578	NN	denotes	insertion
T16029	23559-23568	NN	denotes	transgene
T16028	23579-23584	NNS	denotes	sites
T16027	23550-23558	JJ	denotes	multiple
T16026	23538-23545	NNS	denotes	animals
T16025	23534-23537	DT	denotes	the
T16024	23531-23533	IN	denotes	of
T16023	23526-23530	JJ	denotes	many
T16022	23546-23549	VBD	denotes	had
T16021	23521-23525	IN	denotes	that
T16020	23503-23511	NNS	denotes	founders
T16019	23497-23502	DT	denotes	these
T16018	23494-23496	IN	denotes	of
T16017	23512-23520	VBD	denotes	revealed
T16016	23485-23493	NN	denotes	breeding
T16015	23474-23484	JJ	denotes	Subsequent
T16014	23473-23601	sentence	denotes	Subsequent breeding of these founders revealed that many of the animals had multiple transgene insertion sites that segregated.
T16013	23472-23473	.	denotes	.
T16012	23455-23463	JJ	denotes	positive
T16011	23445-23454	NN	denotes	transgene
T16010	23464-23472	NNS	denotes	founders
T16009	23443-23444	CD	denotes	8
T16008	23431-23433	PRP	denotes	we
T16007	23429-23431	,	denotes	,
T16006	23419-23429	NNP	denotes	Cincinnati
T16005	23416-23418	IN	denotes	of
T16004	23405-23415	NNP	denotes	University
T16003	23401-23404	DT	denotes	the
T16002	23398-23400	IN	denotes	at
T16001	23387-23397	NNS	denotes	injections
T16000	23383-23386	DT	denotes	the
T15999	23434-23442	VBD	denotes	obtained
T15998	23378-23382	IN	denotes	From
T15997	23377-23473	sentence	denotes	From the injections at the University of Cincinnati, we obtained 8 transgene positive founders.
T15996	23376-23377	.	denotes	.
T15995	23375-23376	-RRB-	denotes	)
T15994	23374-23375	NN	denotes	D
T15993	23372-23373	CC	denotes	&
T15992	23370-23372	,	denotes	,
T15991	23369-23370	NN	denotes	B
T15990	23367-23369	,	denotes	,
T15989	23360-23365	NNS	denotes	Lines
T15988	23366-23367	NN	denotes	A
T15987	23359-23360	-LRB-	denotes	(
T15986	23342-23352	JJ	denotes	transgenic
T15985	23332-23341	JJ	denotes	different
T15984	23353-23358	NNS	denotes	lines
T15983	23330-23331	CD	denotes	3
T15982	23327-23329	IN	denotes	of
T15981	23316-23326	NN	denotes	generation
T15980	23312-23315	DT	denotes	the
T15979	23309-23311	IN	denotes	to
T15978	23305-23308	VBD	denotes	led
T15977	23300-23304	WDT	denotes	that
T15976	23284-23288	VBD	denotes	were
T15975	23266-23274	JJ	denotes	positive
T15974	23256-23265	NN	denotes	transgene
T15973	23275-23283	NNS	denotes	founders
T15972	23254-23255	CD	denotes	2
T15971	23252-23254	,	denotes	,
T15970	23242-23252	NNP	denotes	Pittsburgh
T15969	23239-23241	IN	denotes	of
T15968	23228-23238	NNP	denotes	University
T15967	23224-23227	DT	denotes	the
T15966	23221-23223	IN	denotes	at
T15965	23210-23220	NNS	denotes	injections
T15964	23289-23299	VBN	denotes	identified
T15963	23205-23209	IN	denotes	From
T15962	23204-23377	sentence	denotes	From injections at the University of Pittsburgh, 2 transgene positive founders were identified that led to the generation of 3 different transgenic lines (Lines A, B, & D).
T15961	23203-23204	.	denotes	.
T15960	23190-23191	HYPH	denotes	-
T12772	20734-20736	IN	denotes	to
T12771	20726-20733	JJ	denotes	similar
T12794	20841-20842	.	denotes	.
T12793	20837-20841	NN	denotes	MSUD
T12792	20829-20836	JJ	denotes	classic
T12791	20815-20822	RB	denotes	closely
T12790	20801-20809	NN	denotes	knockout
T12789	20810-20814	NNS	denotes	mice
T12788	20798-20800	NN	denotes	E2
T12787	20796-20798	,	denotes	,
T12786	20823-20828	VBP	denotes	model
T12785	20792-20796	RB	denotes	Thus
T12784	20791-20842	sentence	denotes	Thus, E2 knockout mice closely model classic MSUD.
T12783	20790-20791	.	denotes	.
T12782	20786-20790	NN	denotes	MSUD
T12781	20783-20785	IN	denotes	of
T12780	20770-20777	JJ	denotes	classic
T12779	20778-20782	NN	denotes	form
T12778	20766-20769	DT	denotes	the
T12777	20761-20765	IN	denotes	with
T12776	20754-20760	NNS	denotes	humans
T12775	20751-20753	IN	denotes	in
T12774	20742-20750	VBN	denotes	observed
T12773	20737-20741	DT	denotes	that
T12770	20715-20725	RB	denotes	remarkably
T12769	20711-20714	VBP	denotes	are
T12768	20700-20710	NNS	denotes	phenotypes
T12767	20694-20699	DT	denotes	These
T12766	20693-20791	sentence	denotes	These phenotypes are remarkably similar to that observed in humans with the classic form of MSUD.
T12765	20692-20693	.	denotes	.
T12764	20683-20692	NN	denotes	lethality
T12763	20674-20682	JJ	denotes	neonatal
T12762	20671-20673	IN	denotes	in
T12761	20653-20663	RB	denotes	ultimately
T12760	20664-20670	VBP	denotes	result
T12759	20630-20639	JJ	denotes	metabolic
T12758	20640-20652	NNS	denotes	derangements
T12757	20624-20629	DT	denotes	These
T12756	20623-20693	sentence	denotes	These metabolic derangements ultimately result in neonatal lethality.
T12755	20622-20623	.	denotes	.
T12754	20617-20622	NN	denotes	urine
T12753	20613-20616	CC	denotes	and
T12752	20607-20612	NN	denotes	blood
T12751	20603-20606	DT	denotes	the
T12750	20600-20602	IN	denotes	in
T12749	20595-20599	NN	denotes	BCAA
T12748	20592-20594	IN	denotes	of
T12747	20585-20591	NNS	denotes	levels
T12746	20576-20584	VBN	denotes	elevated
T12745	20567-20575	RB	denotes	markedly
T12744	20562-20566	VBP	denotes	have
T12743	20558-20561	CC	denotes	and
T12742	20556-20558	,	denotes	,
T12741	20540-20556	NN	denotes	immunoreactivity
T12740	20537-20539	NN	denotes	E2
T12739	20535-20537	,	denotes	,
T12738	20517-20526	JJ	denotes	enzymatic
T3318	78-88	NN	denotes	deficiency
T3319	89-91	IN	denotes	of
T3320	92-100	VBN	denotes	branched
T3321	101-106	NN	denotes	chain
T3322	100-101	HYPH	denotes	-
T3323	117-130	NN	denotes	dehydrogenase
T3324	107-111	NN	denotes	keto
T3325	112-116	NN	denotes	acid
T3326	131-132	-LRB-	denotes	(
T3327	132-137	NN	denotes	BCKDH
T3328	137-138	-RRB-	denotes	)
T3329	138-140	,	denotes	,
T3330	140-141	DT	denotes	a
T3331	168-175	NN	denotes	complex
T3332	142-155	JJ	denotes	mitochondrial
T3333	156-167	NN	denotes	multienzyme
T3334	176-187	JJ	denotes	responsible
T3335	188-191	IN	denotes	for
T3336	192-195	DT	denotes	the
T3337	206-221	NN	denotes	decarboxylation
T3338	196-205	JJ	denotes	oxidative
T3339	222-224	IN	denotes	of
T3340	225-233	VBN	denotes	branched
T3341	234-239	NN	denotes	chain
T3342	233-234	HYPH	denotes	-
T3343	245-250	NNS	denotes	acids
T3344	240-244	NN	denotes	keto
T3345	251-258	VBN	denotes	derived
T3346	259-263	IN	denotes	from
T3347	264-272	VBN	denotes	branched
T3348	273-278	NN	denotes	chain
T3349	272-273	HYPH	denotes	-
T3350	285-290	NNS	denotes	acids
T3351	279-284	NN	denotes	amino
T3352	291-292	-LRB-	denotes	(
T3353	292-296	NN	denotes	BCAA
T3354	296-297	-RRB-	denotes	)
T3355	297-299	,	denotes	,
T3356	299-306	NN	denotes	leucine
T3357	306-308	,	denotes	,
T3358	308-318	NN	denotes	isoleucine
T3359	319-322	CC	denotes	and
T3360	323-329	NN	denotes	valine
T3361	330-331	-LRB-	denotes	(
T3362	343-346	VB	denotes	see
T3363	331-334	IN	denotes	for
T3364	335-341	NN	denotes	review
T3365	341-343	,	denotes	,
T3366	346-348	:	denotes	:
T3367	348-349	-LRB-	denotes	[
T3368	349-350	CD	denotes	1
T3369	350-351	-RRB-	denotes	]
T3370	351-352	-RRB-	denotes	)
T3371	352-353	.	denotes	.
T3372	353-497	sentence	denotes	Patients with MSUD, depending on the mutation, show variable degrees of enzyme deficiency leading to several different clinical phenotypes [1].
T3373	354-362	NNS	denotes	Patients
T3374	401-405	VBP	denotes	show
T3375	363-367	IN	denotes	with
T3376	368-372	NN	denotes	MSUD
T3377	372-374	,	denotes	,
T3378	374-383	VBG	denotes	depending
T3379	384-386	IN	denotes	on
T3380	387-390	DT	denotes	the
T3381	391-399	NN	denotes	mutation
T3382	399-401	,	denotes	,
T3383	406-414	JJ	denotes	variable
T3384	415-422	NNS	denotes	degrees
T3385	423-425	IN	denotes	of
T3386	426-432	NN	denotes	enzyme
T3387	433-443	NN	denotes	deficiency
T3388	444-451	VBG	denotes	leading
T3389	452-454	IN	denotes	to
T3390	455-462	JJ	denotes	several
T3391	482-492	NNS	denotes	phenotypes
T3392	463-472	JJ	denotes	different
T3393	473-481	JJ	denotes	clinical
T3394	493-494	-LRB-	denotes	[
T3395	494-495	CD	denotes	1
T3396	495-496	-RRB-	denotes	]
T3397	496-497	.	denotes	.
T3398	497-625	sentence	denotes	Approximately 75% of MSUD patients have the classic form of the disease with BCKDH activity in the range of 0–2% of normal [1].
T3399	498-511	RB	denotes	Approximately
T3400	512-514	CD	denotes	75
T3401	514-515	NN	denotes	%
T3402	533-537	VBP	denotes	have
T3403	516-518	IN	denotes	of
T3404	519-523	NN	denotes	MSUD
T3405	524-532	NNS	denotes	patients
T3406	538-541	DT	denotes	the
T3407	550-554	NN	denotes	form
T3408	542-549	JJ	denotes	classic
T3409	555-557	IN	denotes	of
T3410	558-561	DT	denotes	the
T3411	562-569	NN	denotes	disease
T3412	570-574	IN	denotes	with
T3413	575-580	NN	denotes	BCKDH
T3414	581-589	NN	denotes	activity
T3415	590-592	IN	denotes	in
T3416	593-596	DT	denotes	the
T3417	597-602	NN	denotes	range
T3418	603-605	IN	denotes	of
T3419	606-607	CD	denotes	0
T3420	608-609	CD	denotes	2
T3421	607-608	SYM	denotes	–
T3422	609-610	NN	denotes	%
T3423	611-613	IN	denotes	of
T3424	614-620	JJ	denotes	normal
T3425	621-622	-LRB-	denotes	[
T3426	622-623	CD	denotes	1
T3427	623-624	-RRB-	denotes	]
T3428	624-625	.	denotes	.
T3429	625-714	sentence	denotes	These patients show markedly elevated levels of BCAA in blood and other body fluids [1].
T3430	626-631	DT	denotes	These
T3431	632-640	NNS	denotes	patients
T3432	641-645	VBP	denotes	show
T3433	646-654	RB	denotes	markedly
T3434	655-663	VBN	denotes	elevated
T3435	664-670	NNS	denotes	levels
T3436	671-673	IN	denotes	of
T3437	674-678	NN	denotes	BCAA
T3438	679-681	IN	denotes	in
T3439	682-687	NN	denotes	blood
T3440	688-691	CC	denotes	and
T3441	692-697	JJ	denotes	other
T3442	703-709	NNS	denotes	fluids
T3443	698-702	NN	denotes	body
T3444	710-711	-LRB-	denotes	[
T3445	711-712	CD	denotes	1
T3446	712-713	-RRB-	denotes	]
T3447	713-714	.	denotes	.
T3448	714-781	sentence	denotes	Besides the classic form, there are other variants of the disease.
T3449	715-722	IN	denotes	Besides
T3450	747-750	VBP	denotes	are
T3451	723-726	DT	denotes	the
T3452	735-739	NN	denotes	form
T3453	727-734	JJ	denotes	classic
T3454	739-741	,	denotes	,
T3455	741-746	EX	denotes	there
T3456	751-756	JJ	denotes	other
T3457	757-765	NNS	denotes	variants
T3458	766-768	IN	denotes	of
T3459	769-772	DT	denotes	the
T3460	773-780	NN	denotes	disease
T3461	780-781	.	denotes	.
T3462	781-885	sentence	denotes	Patients with the intermediate form of the disease show BCKDH activity in the range of 3–30% of normal.
T3463	782-790	NNS	denotes	Patients
T3464	833-837	VBP	denotes	show
T3465	791-795	IN	denotes	with
T3466	796-799	DT	denotes	the
T3467	813-817	NN	denotes	form
T3468	800-812	JJ	denotes	intermediate
T3469	818-820	IN	denotes	of
T3470	821-824	DT	denotes	the
T3471	825-832	NN	denotes	disease
T3472	838-843	NN	denotes	BCKDH
T3473	844-852	NN	denotes	activity
T3474	853-855	IN	denotes	in
T3475	856-859	DT	denotes	the
T3476	860-865	NN	denotes	range
T3477	866-868	IN	denotes	of
T3478	869-870	CD	denotes	3
T3479	871-873	CD	denotes	30
T3480	870-871	SYM	denotes	–
T3481	873-874	NN	denotes	%
T3482	875-877	IN	denotes	of
T3483	878-884	JJ	denotes	normal
T3484	884-885	.	denotes	.
T3485	885-995	sentence	denotes	In such patients the onset of the disease is delayed, but there are persistently elevated levels of BCAA [1].
T3486	886-888	IN	denotes	In
T3487	931-938	VBN	denotes	delayed
T3488	889-893	JJ	denotes	such
T3489	894-902	NNS	denotes	patients
T3490	903-906	DT	denotes	the
T3491	907-912	NN	denotes	onset
T3492	913-915	IN	denotes	of
T3493	916-919	DT	denotes	the
T3494	920-927	NN	denotes	disease
T3495	928-930	VBZ	denotes	is
T3496	938-940	,	denotes	,
T3497	940-943	CC	denotes	but
T3498	944-949	EX	denotes	there
T3499	950-953	VBP	denotes	are
T3500	954-966	RB	denotes	persistently
T3501	967-975	VBN	denotes	elevated
T3502	976-982	NNS	denotes	levels
T3503	983-985	IN	denotes	of
T3504	986-990	NN	denotes	BCAA
T3505	991-992	-LRB-	denotes	[
T3506	992-993	CD	denotes	1
T3507	993-994	-RRB-	denotes	]
T3508	994-995	.	denotes	.
T3509	995-1153	sentence	denotes	Patients with the intermittent form of MSUD show BCKDH activity in the range of 5–20% and during the asymptomatic phase the blood BCAA levels are normal [1].
T3510	996-1004	NNS	denotes	Patients
T3511	1040-1044	VBP	denotes	show
T3512	1005-1009	IN	denotes	with
T3513	1010-1013	DT	denotes	the
T3514	1027-1031	NN	denotes	form
T3515	1014-1026	JJ	denotes	intermittent
T3516	1032-1034	IN	denotes	of
T3517	1035-1039	NN	denotes	MSUD
T3518	1045-1050	NN	denotes	BCKDH
T3519	1051-1059	NN	denotes	activity
T3520	1060-1062	IN	denotes	in
T3521	1063-1066	DT	denotes	the
T3522	1067-1072	NN	denotes	range
T3523	1073-1075	IN	denotes	of
T3524	1076-1077	CD	denotes	5
T3525	1078-1080	CD	denotes	20
T3526	1077-1078	SYM	denotes	–
T3527	1080-1081	NN	denotes	%
T3528	1082-1085	CC	denotes	and
T3529	1086-1092	IN	denotes	during
T3530	1138-1141	VBP	denotes	are
T3531	1093-1096	DT	denotes	the
T3532	1110-1115	NN	denotes	phase
T3533	1097-1109	JJ	denotes	asymptomatic
T3534	1116-1119	DT	denotes	the
T3535	1131-1137	NNS	denotes	levels
T3536	1120-1125	NN	denotes	blood
T3537	1126-1130	NN	denotes	BCAA
T3538	1142-1148	JJ	denotes	normal
T3539	1149-1150	-LRB-	denotes	[
T3540	1150-1151	CD	denotes	1
T3541	1151-1152	-RRB-	denotes	]
T3542	1152-1153	.	denotes	.
T3543	1153-1352	sentence	denotes	The overall incidence of MSUD in the general population is 1:185,000 [1], and in certain population groups, such as Mennonites of Pennsylvania, the incidence is estimated to be as high as 1:176 [2].
T3544	1154-1157	DT	denotes	The
T3545	1166-1175	NN	denotes	incidence
T3546	1158-1165	JJ	denotes	overall
T3547	1210-1212	VBZ	denotes	is
T3548	1176-1178	IN	denotes	of
T3549	1179-1183	NN	denotes	MSUD
T3550	1184-1186	IN	denotes	in
T3551	1187-1190	DT	denotes	the
T3552	1199-1209	NN	denotes	population
T3553	1191-1198	JJ	denotes	general
T3554	1213-1214	CD	denotes	1
T3555	1215-1222	CD	denotes	185,000
T3556	1214-1215	SYM	denotes	:
T3557	1223-1224	-LRB-	denotes	[
T3558	1224-1225	CD	denotes	1
T3559	1225-1226	-RRB-	denotes	]
T3560	1226-1228	,	denotes	,
T3561	1228-1231	CC	denotes	and
T3562	1232-1234	IN	denotes	in
T3563	1315-1324	VBN	denotes	estimated
T3564	1235-1242	JJ	denotes	certain
T3565	1254-1260	NNS	denotes	groups
T3566	1243-1253	NN	denotes	population
T3567	1260-1262	,	denotes	,
T3568	1262-1266	JJ	denotes	such
T3569	1267-1269	IN	denotes	as
T3570	1270-1280	NNS	denotes	Mennonites
T3571	1281-1283	IN	denotes	of
T3572	1284-1296	NNP	denotes	Pennsylvania
T3573	1296-1298	,	denotes	,
T3574	1298-1301	DT	denotes	the
T3575	1302-1311	NN	denotes	incidence
T3576	1312-1314	VBZ	denotes	is
T3577	1325-1327	TO	denotes	to
T3578	1328-1330	VB	denotes	be
T3579	1331-1333	IN	denotes	as
T3580	1334-1338	JJ	denotes	high
T3581	1339-1341	IN	denotes	as
T3582	1342-1343	CD	denotes	1
T3583	1344-1347	CD	denotes	176
T3584	1343-1344	SYM	denotes	:
T3585	1348-1349	-LRB-	denotes	[
T3586	1349-1350	CD	denotes	2
T3587	1350-1351	-RRB-	denotes	]
T3588	1351-1352	.	denotes	.
T3589	1352-1536	sentence	denotes	The BCKDH complex, the deficient enzyme in MSUD, consists of three catalytic proteins, a decarboxylase (E1), a dihydrolipoyl transacylase (E2), and a dihydrolipoyl dehydrogenase (E3).
T3590	1353-1356	DT	denotes	The
T3591	1363-1370	NN	denotes	complex
T3592	1357-1362	NN	denotes	BCKDH
T3593	1402-1410	VBZ	denotes	consists
T3594	1370-1372	,	denotes	,
T3595	1372-1375	DT	denotes	the
T3596	1386-1392	NN	denotes	enzyme
T3597	1376-1385	JJ	denotes	deficient
T3598	1393-1395	IN	denotes	in
T3599	1396-1400	NN	denotes	MSUD
T3600	1400-1402	,	denotes	,
T3601	1411-1413	IN	denotes	of
T3602	1414-1419	CD	denotes	three
T3603	1430-1438	NN	denotes	proteins
T3604	1420-1429	JJ	denotes	catalytic
T3605	1438-1440	,	denotes	,
T3606	1440-1441	DT	denotes	a
T3607	1442-1455	NN	denotes	decarboxylase
T3608	1456-1457	-LRB-	denotes	(
T3609	1457-1459	NN	denotes	E1
T3610	1459-1460	-RRB-	denotes	)
T3611	1460-1462	,	denotes	,
T3612	1462-1463	DT	denotes	a
T3613	1478-1490	NN	denotes	transacylase
T3614	1464-1477	NN	denotes	dihydrolipoyl
T3615	1491-1492	-LRB-	denotes	(
T3616	1492-1494	NN	denotes	E2
T3617	1494-1495	-RRB-	denotes	)
T3618	1495-1497	,	denotes	,
T3619	1497-1500	CC	denotes	and
T3620	1501-1502	DT	denotes	a
T3621	1517-1530	NN	denotes	dehydrogenase
T3622	1503-1516	NN	denotes	dihydrolipoyl
T3623	1531-1532	-LRB-	denotes	(
T3624	1532-1534	NN	denotes	E3
T3625	1534-1535	-RRB-	denotes	)
T3626	1535-1536	.	denotes	.
T3627	1536-1615	sentence	denotes	The E1 component is a heterotetramer composed of two α and two β subunits [3].
T3628	1537-1540	DT	denotes	The
T3629	1544-1553	NN	denotes	component
T3630	1541-1543	NN	denotes	E1
T3631	1554-1556	VBZ	denotes	is
T3632	1557-1558	DT	denotes	a
T3633	1559-1573	NN	denotes	heterotetramer
T3634	1574-1582	VBN	denotes	composed
T3635	1583-1585	IN	denotes	of
T3636	1586-1589	CD	denotes	two
T3637	1590-1591	NN	denotes	α
T3638	1602-1610	NNS	denotes	subunits
T3639	1592-1595	CC	denotes	and
T3640	1596-1599	CD	denotes	two
T3641	1600-1601	NN	denotes	β
T3642	1611-1612	-LRB-	denotes	[
T3643	1612-1613	CD	denotes	3
T3644	1613-1614	-RRB-	denotes	]
T3645	1614-1615	.	denotes	.
T3646	1615-1784	sentence	denotes	The E1 and E2 components are specific to BCKDH, whereas E3 is also used by pyruvate and α-ketoglutarate dehydrogenase complexes [3] and the glycine cleavage system [4].
T3647	1616-1619	DT	denotes	The
T3648	1630-1640	NNS	denotes	components
T3649	1620-1622	NN	denotes	E1
T3650	1623-1626	CC	denotes	and
T3651	1627-1629	NN	denotes	E2
T3652	1641-1644	VBP	denotes	are
T3653	1645-1653	JJ	denotes	specific
T3654	1654-1656	IN	denotes	to
T3655	1657-1662	NN	denotes	BCKDH
T3656	1662-1664	,	denotes	,
T3657	1664-1671	IN	denotes	whereas
T3658	1683-1687	VBN	denotes	used
T3659	1672-1674	NN	denotes	E3
T3660	1675-1677	VBZ	denotes	is
T3661	1678-1682	RB	denotes	also
T3662	1688-1690	IN	denotes	by
T3663	1691-1699	NN	denotes	pyruvate
T3664	1734-1743	NNS	denotes	complexes
T3665	1700-1703	CC	denotes	and
T3666	1704-1705	NN	denotes	α
T3667	1706-1719	NN	denotes	ketoglutarate
T3668	1705-1706	HYPH	denotes	-
T3669	1720-1733	NN	denotes	dehydrogenase
T3670	1744-1745	-LRB-	denotes	[
T3671	1745-1746	CD	denotes	3
T3672	1746-1747	-RRB-	denotes	]
T3673	1748-1751	CC	denotes	and
T3674	1752-1755	DT	denotes	the
T3675	1773-1779	NN	denotes	system
T3676	1756-1763	NN	denotes	glycine
T3677	1764-1772	NN	denotes	cleavage
T3678	1780-1781	-LRB-	denotes	[
T3679	1781-1782	CD	denotes	4
T3680	1782-1783	-RRB-	denotes	]
T3681	1783-1784	.	denotes	.
T3682	1784-2027	sentence	denotes	BCKDH is also associated with two regulatory proteins, a specific kinase and a phosphatase which regulate the activity of this enzyme through a phosphorylation (inactivation) and dephosphorylation (activation) cycle of the E1 α subunit [5,6].
T3683	1785-1790	NN	denotes	BCKDH
T3684	1799-1809	VBN	denotes	associated
T3685	1791-1793	VBZ	denotes	is
T3686	1794-1798	RB	denotes	also
T3687	1810-1814	IN	denotes	with
T3688	1815-1818	CD	denotes	two
T3689	1830-1838	NN	denotes	proteins
T3690	1819-1829	JJ	denotes	regulatory
T3691	1838-1840	,	denotes	,
T3692	1840-1841	DT	denotes	a
T3693	1851-1857	NN	denotes	kinase
T3694	1842-1850	JJ	denotes	specific
T3695	1858-1861	CC	denotes	and
T3696	1862-1863	DT	denotes	a
T3697	1864-1875	NN	denotes	phosphatase
T3698	1876-1881	WDT	denotes	which
T3699	1882-1890	VBP	denotes	regulate
T3700	1891-1894	DT	denotes	the
T3701	1895-1903	NN	denotes	activity
T3702	1904-1906	IN	denotes	of
T3703	1907-1911	DT	denotes	this
T3704	1912-1918	NN	denotes	enzyme
T3705	1919-1926	IN	denotes	through
T3706	1927-1928	DT	denotes	a
T3707	1995-2000	NN	denotes	cycle
T3708	1929-1944	NN	denotes	phosphorylation
T3709	1945-1946	-LRB-	denotes	(
T3710	1946-1958	NN	denotes	inactivation
T3711	1958-1959	-RRB-	denotes	)
T3712	1960-1963	CC	denotes	and
T3713	1964-1981	NN	denotes	dephosphorylation
T3714	1982-1983	-LRB-	denotes	(
T3715	1983-1993	NN	denotes	activation
T3716	1993-1994	-RRB-	denotes	)
T3717	2001-2003	IN	denotes	of
T3718	2004-2007	DT	denotes	the
T3719	2013-2020	NN	denotes	subunit
T3720	2008-2010	NN	denotes	E1
T3721	2011-2012	NN	denotes	α
T3722	2021-2022	-LRB-	denotes	[
T3723	2024-2025	CD	denotes	6
T3724	2022-2023	CD	denotes	5
T3725	2023-2024	,	denotes	,
T3726	2025-2026	-RRB-	denotes	]
T3727	2026-2027	.	denotes	.
T3728	2027-2195	sentence	denotes	Mutations in the genes of the E1 and E2 subunits of BCKDH have been described, however, the majority of MSUD mutations identified thus far are in the E2 subunit [1,7].
T3729	2028-2037	NNS	denotes	Mutations
T3730	2096-2105	VBN	denotes	described
T3731	2038-2040	IN	denotes	in
T3732	2041-2044	DT	denotes	the
T3733	2045-2050	NNS	denotes	genes
T3734	2051-2053	IN	denotes	of
T3735	2054-2057	DT	denotes	the
T3736	2068-2076	NNS	denotes	subunits
T3737	2058-2060	NN	denotes	E1
T3738	2061-2064	CC	denotes	and
T3739	2065-2067	NN	denotes	E2
T3740	2077-2079	IN	denotes	of
T3741	2080-2085	NN	denotes	BCKDH
T3742	2086-2090	VBP	denotes	have
T3743	2091-2095	VBN	denotes	been
T3744	2167-2170	VBP	denotes	are
T3745	2105-2107	,	denotes	,
T3746	2107-2114	RB	denotes	however
T3747	2114-2116	,	denotes	,
T3748	2116-2119	DT	denotes	the
T3749	2120-2128	NN	denotes	majority
T3750	2129-2131	IN	denotes	of
T3751	2132-2136	NN	denotes	MSUD
T3752	2137-2146	NNS	denotes	mutations
T3753	2147-2157	VBN	denotes	identified
T3754	2158-2162	RB	denotes	thus
T3755	2163-2166	RB	denotes	far
T3756	2171-2173	IN	denotes	in
T3757	2174-2177	DT	denotes	the
T3758	2181-2188	NN	denotes	subunit
T3759	2178-2180	NN	denotes	E2
T3760	2189-2190	-LRB-	denotes	[
T3761	2192-2193	CD	denotes	7
T3762	2190-2191	CD	denotes	1
T3763	2191-2192	,	denotes	,
T3764	2193-2194	-RRB-	denotes	]
T3765	2194-2195	.	denotes	.
T3766	2195-2302	sentence	denotes	To date, cases of MSUD have not been associated with defects in the regulatory kinase and phosphatase [1].
T3767	2196-2198	IN	denotes	To
T3768	2233-2243	VBN	denotes	associated
T3769	2199-2203	NN	denotes	date
T3770	2203-2205	,	denotes	,
T3771	2205-2210	NNS	denotes	cases
T3772	2211-2213	IN	denotes	of
T3773	2214-2218	NN	denotes	MSUD
T3774	2219-2223	VBP	denotes	have
T3775	2224-2227	RB	denotes	not
T3776	2228-2232	VBN	denotes	been
T3777	2244-2248	IN	denotes	with
T3778	2249-2256	NNS	denotes	defects
T3779	2257-2259	IN	denotes	in
T3780	2260-2263	DT	denotes	the
T3781	2275-2281	NN	denotes	kinase
T3782	2264-2274	JJ	denotes	regulatory
T3783	2282-2285	CC	denotes	and
T3784	2286-2297	NN	denotes	phosphatase
T3785	2298-2299	-LRB-	denotes	[
T3786	2299-2300	CD	denotes	1
T3787	2300-2301	-RRB-	denotes	]
T3788	2301-2302	.	denotes	.
T3789	2302-2412	sentence	denotes	Current management of MSUD patients relies on a strict lifelong dietary restriction of protein or BCAA [1,8].
T3790	2303-2310	JJ	denotes	Current
T3791	2311-2321	NN	denotes	management
T3792	2339-2345	VBZ	denotes	relies
T3793	2322-2324	IN	denotes	of
T3794	2325-2329	NN	denotes	MSUD
T3795	2330-2338	NNS	denotes	patients
T3796	2346-2348	IN	denotes	on
T3797	2349-2350	DT	denotes	a
T3798	2375-2386	NN	denotes	restriction
T3799	2351-2357	JJ	denotes	strict
T3800	2358-2366	JJ	denotes	lifelong
T3801	2367-2374	JJ	denotes	dietary
T3802	2387-2389	IN	denotes	of
T3803	2390-2397	NN	denotes	protein
T3804	2398-2400	CC	denotes	or
T3805	2401-2405	NN	denotes	BCAA
T3806	2406-2407	-LRB-	denotes	[
T3807	2409-2410	CD	denotes	8
T3808	2407-2408	CD	denotes	1
T3809	2408-2409	,	denotes	,
T3810	2410-2411	-RRB-	denotes	]
T3811	2411-2412	.	denotes	.
T3812	2412-2588	sentence	denotes	Such a dietary management of the disease, however, is not entirely satisfactory especially in times of metabolic decompensation due to infection, injuries and other stressors.
T3813	2413-2417	PDT	denotes	Such
T3814	2428-2438	NN	denotes	management
T3815	2418-2419	DT	denotes	a
T3816	2420-2427	JJ	denotes	dietary
T3817	2464-2466	VBZ	denotes	is
T3818	2439-2441	IN	denotes	of
T3819	2442-2445	DT	denotes	the
T3820	2446-2453	NN	denotes	disease
T3821	2453-2455	,	denotes	,
T3822	2455-2462	RB	denotes	however
T3823	2462-2464	,	denotes	,
T3824	2467-2470	RB	denotes	not
T3825	2471-2479	RB	denotes	entirely
T3826	2480-2492	JJ	denotes	satisfactory
T3827	2493-2503	RB	denotes	especially
T3828	2504-2506	IN	denotes	in
T3829	2507-2512	NNS	denotes	times
T3830	2513-2515	IN	denotes	of
T3831	2516-2525	JJ	denotes	metabolic
T3832	2526-2540	NN	denotes	decompensation
T3833	2541-2544	IN	denotes	due
T3834	2545-2547	IN	denotes	to
T3835	2548-2557	NN	denotes	infection
T3836	2557-2559	,	denotes	,
T3837	2559-2567	NNS	denotes	injuries
T3838	2568-2571	CC	denotes	and
T3839	2572-2577	JJ	denotes	other
T3840	2578-2587	NNS	denotes	stressors
T3841	2587-2588	.	denotes	.
T3842	2588-2744	sentence	denotes	In spite of dietary intervention, there is significant mortality associated with MSUD and there is a high incidence of mental retardation in survivors [9].
T3843	2589-2591	IN	denotes	In
T3844	2629-2631	VBZ	denotes	is
T3845	2592-2597	NN	denotes	spite
T3846	2598-2600	IN	denotes	of
T3847	2601-2608	JJ	denotes	dietary
T3848	2609-2621	NN	denotes	intervention
T3849	2621-2623	,	denotes	,
T3850	2623-2628	EX	denotes	there
T3851	2632-2643	JJ	denotes	significant
T3852	2644-2653	NN	denotes	mortality
T3853	2654-2664	VBN	denotes	associated
T3854	2665-2669	IN	denotes	with
T3855	2670-2674	NN	denotes	MSUD
T3856	2675-2678	CC	denotes	and
T3857	2679-2684	EX	denotes	there
T3858	2685-2687	VBZ	denotes	is
T3859	2688-2689	DT	denotes	a
T3860	2695-2704	NN	denotes	incidence
T3861	2690-2694	JJ	denotes	high
T3862	2705-2707	IN	denotes	of
T3863	2708-2714	JJ	denotes	mental
T3864	2715-2726	NN	denotes	retardation
T3865	2727-2729	IN	denotes	in
T3866	2730-2739	NNS	denotes	survivors
T3867	2740-2741	-LRB-	denotes	[
T3868	2741-2742	CD	denotes	9
T3869	2742-2743	-RRB-	denotes	]
T3870	2743-2744	.	denotes	.
T3871	2744-2958	sentence	denotes	Because of the central role of the liver in amino acid metabolism and moderate/high levels of BCKDH activity in human liver [10-12], a few cases of MSUD have recently been treated by liver transplantation [13-16].
T3872	2745-2752	IN	denotes	Because
T3873	2917-2924	VBN	denotes	treated
T3874	2753-2755	IN	denotes	of
T3875	2756-2759	DT	denotes	the
T3876	2768-2772	NN	denotes	role
T3877	2760-2767	JJ	denotes	central
T3878	2773-2775	IN	denotes	of
T3879	2776-2779	DT	denotes	the
T3880	2780-2785	NN	denotes	liver
T3881	2786-2788	IN	denotes	in
T3882	2789-2794	NN	denotes	amino
T3883	2795-2799	NN	denotes	acid
T3884	2800-2810	NN	denotes	metabolism
T3885	2811-2814	CC	denotes	and
T3886	2815-2823	JJ	denotes	moderate
T3887	2824-2828	JJ	denotes	high
T3888	2823-2824	SYM	denotes	/
T3889	2829-2835	NNS	denotes	levels
T3890	2836-2838	IN	denotes	of
T3891	2839-2844	NN	denotes	BCKDH
T3892	2845-2853	NN	denotes	activity
T3893	2854-2856	IN	denotes	in
T3894	2857-2862	JJ	denotes	human
T3895	2863-2868	NN	denotes	liver
T3896	2869-2870	-LRB-	denotes	[
T3897	2870-2872	CD	denotes	10
T3898	2872-2873	SYM	denotes	-
T3899	2873-2875	CD	denotes	12
T3900	2875-2876	-RRB-	denotes	]
T3901	2876-2878	,	denotes	,
T3902	2878-2879	DT	denotes	a
T3903	2884-2889	NNS	denotes	cases
T3904	2880-2883	JJ	denotes	few
T3905	2890-2892	IN	denotes	of
T3906	2893-2897	NN	denotes	MSUD
T3907	2898-2902	VBP	denotes	have
T3908	2903-2911	RB	denotes	recently
T3909	2912-2916	VBN	denotes	been
T3910	2925-2927	IN	denotes	by
T3911	2928-2933	NN	denotes	liver
T3912	2934-2949	NN	denotes	transplantation
T3913	2950-2951	-LRB-	denotes	[
T3914	2951-2953	CD	denotes	13
T3915	2953-2954	SYM	denotes	-
T3916	2954-2956	CD	denotes	16
T3917	2956-2957	-RRB-	denotes	]
T3918	2957-2958	.	denotes	.
T3919	2958-3078	sentence	denotes	While the short-term outcome of liver transplantation is encouraging, long-term effects of this approach are not known.
T3920	2959-2964	IN	denotes	While
T3921	3013-3015	VBZ	denotes	is
T3922	2965-2968	DT	denotes	the
T3923	2980-2987	NN	denotes	outcome
T3924	2969-2974	JJ	denotes	short
T3925	2975-2979	NN	denotes	term
T3926	2974-2975	HYPH	denotes	-
T3927	2988-2990	IN	denotes	of
T3928	2991-2996	NN	denotes	liver
T3929	2997-3012	NN	denotes	transplantation
T3930	3072-3077	VBN	denotes	known
T3931	3016-3027	JJ	denotes	encouraging
T3932	3027-3029	,	denotes	,
T3933	3029-3033	JJ	denotes	long
T3934	3034-3038	NN	denotes	term
T3935	3033-3034	HYPH	denotes	-
T3936	3039-3046	NNS	denotes	effects
T3937	3047-3049	IN	denotes	of
T3938	3050-3054	DT	denotes	this
T3939	3055-3063	NN	denotes	approach
T3940	3064-3067	VBP	denotes	are
T3941	3068-3071	RB	denotes	not
T3942	3077-3078	.	denotes	.
T3943	3078-3217	sentence	denotes	However, these patients are now required to take immunosuppressant drugs for the rest of their lives, often with undesirable side effects.
T3944	3079-3086	RB	denotes	However
T3945	3111-3119	VBN	denotes	required
T3946	3086-3088	,	denotes	,
T3947	3088-3093	DT	denotes	these
T3948	3094-3102	NNS	denotes	patients
T3949	3103-3106	VBP	denotes	are
T3950	3107-3110	RB	denotes	now
T3951	3120-3122	TO	denotes	to
T3952	3123-3127	VB	denotes	take
T3953	3128-3145	NN	denotes	immunosuppressant
T3954	3146-3151	NNS	denotes	drugs
T3955	3152-3155	IN	denotes	for
T3956	3156-3159	DT	denotes	the
T3957	3160-3164	NN	denotes	rest
T3958	3165-3167	IN	denotes	of
T3959	3168-3173	PRP$	denotes	their
T3960	3174-3179	NNS	denotes	lives
T3961	3179-3181	,	denotes	,
T3962	3181-3186	RB	denotes	often
T3963	3187-3191	IN	denotes	with
T3964	3192-3203	JJ	denotes	undesirable
T3965	3209-3216	NNS	denotes	effects
T3966	3204-3208	NN	denotes	side
T3967	3216-3217	.	denotes	.
T3968	3217-3394	sentence	denotes	Moreover, the cost associated with liver transplantation and the availability of donor livers are additional limiting factors for the practicality of treatment of this disease.
T3969	3218-3226	RB	denotes	Moreover
T3970	3312-3315	VBP	denotes	are
T3971	3226-3228	,	denotes	,
T3972	3228-3231	DT	denotes	the
T3973	3232-3236	NN	denotes	cost
T3974	3237-3247	VBN	denotes	associated
T3975	3248-3252	IN	denotes	with
T3976	3253-3258	NN	denotes	liver
T3977	3259-3274	NN	denotes	transplantation
T3978	3275-3278	CC	denotes	and
T3979	3279-3282	DT	denotes	the
T3980	3283-3295	NN	denotes	availability
T3981	3296-3298	IN	denotes	of
T3982	3299-3304	NN	denotes	donor
T3983	3305-3311	NNS	denotes	livers
T3984	3316-3326	JJ	denotes	additional
T3985	3336-3343	NNS	denotes	factors
T3986	3327-3335	VBG	denotes	limiting
T3987	3344-3347	IN	denotes	for
T3988	3348-3351	DT	denotes	the
T3989	3352-3364	NN	denotes	practicality
T3990	3365-3367	IN	denotes	of
T3991	3368-3377	NN	denotes	treatment
T3992	3378-3380	IN	denotes	of
T3993	3381-3385	DT	denotes	this
T3994	3386-3393	NN	denotes	disease
T3995	3393-3394	.	denotes	.
T3996	3394-3530	sentence	denotes	Because of the current unsatisfactory options for the treatment of MSUD, there is a need for improved therapies to combat this disease.
T3997	3395-3402	IN	denotes	Because
T3998	3474-3476	VBZ	denotes	is
T3999	3403-3405	IN	denotes	of
T4000	3406-3409	DT	denotes	the
T4001	3433-3440	NNS	denotes	options
T4002	3410-3417	JJ	denotes	current
T4003	3418-3432	JJ	denotes	unsatisfactory
T4004	3441-3444	IN	denotes	for
T4005	3445-3448	DT	denotes	the
T4006	3449-3458	NN	denotes	treatment
T4007	3459-3461	IN	denotes	of
T4008	3462-3466	NN	denotes	MSUD
T4009	3466-3468	,	denotes	,
T4010	3468-3473	EX	denotes	there
T4011	3477-3478	DT	denotes	a
T4012	3479-3483	NN	denotes	need
T4013	3484-3487	IN	denotes	for
T4014	3488-3496	VBN	denotes	improved
T4015	3497-3506	NNS	denotes	therapies
T4016	3507-3509	TO	denotes	to
T4017	3510-3516	VB	denotes	combat
T4018	3517-3521	DT	denotes	this
T4019	3522-3529	NN	denotes	disease
T4020	3529-3530	.	denotes	.
T4021	3530-3669	sentence	denotes	An obstacle to developing novel treatments for MSUD has been the lack of a suitable animal model to perform necessary preclinical studies.
T4022	3531-3533	DT	denotes	An
T4023	3534-3542	NN	denotes	obstacle
T4024	3587-3591	VBN	denotes	been
T4025	3543-3545	IN	denotes	to
T4026	3546-3556	VBG	denotes	developing
T4027	3557-3562	JJ	denotes	novel
T4028	3563-3573	NNS	denotes	treatments
T4029	3574-3577	IN	denotes	for
T4030	3578-3582	NN	denotes	MSUD
T4031	3583-3586	VBZ	denotes	has
T4032	3592-3595	DT	denotes	the
T4033	3596-3600	NN	denotes	lack
T4034	3601-3603	IN	denotes	of
T4035	3604-3605	DT	denotes	a
T4036	3622-3627	NN	denotes	model
T4037	3606-3614	JJ	denotes	suitable
T4038	3615-3621	NN	denotes	animal
T4039	3628-3630	TO	denotes	to
T4040	3631-3638	VB	denotes	perform
T4041	3639-3648	JJ	denotes	necessary
T4042	3661-3668	NNS	denotes	studies
T4043	3649-3660	JJ	denotes	preclinical
T4044	3668-3669	.	denotes	.
T4045	3669-3824	sentence	denotes	Although a Hereford calf model with MSUD has been described [17-19], this model is neither readily available nor practical to perform preclinical studies.
T4046	3670-3678	IN	denotes	Although
T4047	3720-3729	VBN	denotes	described
T4048	3679-3680	DT	denotes	a
T4049	3695-3700	NN	denotes	model
T4050	3681-3689	NNP	denotes	Hereford
T4051	3690-3694	NN	denotes	calf
T4052	3701-3705	IN	denotes	with
T4053	3706-3710	NN	denotes	MSUD
T4054	3711-3714	VBZ	denotes	has
T4055	3715-3719	VBN	denotes	been
T4056	3750-3752	VBZ	denotes	is
T4057	3730-3731	-LRB-	denotes	[
T4058	3731-3733	CD	denotes	17
T4059	3733-3734	SYM	denotes	-
T4060	3734-3736	CD	denotes	19
T4061	3736-3737	-RRB-	denotes	]
T4062	3737-3739	,	denotes	,
T4063	3739-3743	DT	denotes	this
T4064	3744-3749	NN	denotes	model
T4065	3753-3760	CC	denotes	neither
T4066	3769-3778	JJ	denotes	available
T4067	3761-3768	RB	denotes	readily
T4068	3779-3782	CC	denotes	nor
T4069	3783-3792	JJ	denotes	practical
T4070	3793-3795	TO	denotes	to
T4071	3796-3803	VB	denotes	perform
T4072	3804-3815	JJ	denotes	preclinical
T4073	3816-3823	NNS	denotes	studies
T4074	3823-3824	.	denotes	.
T4075	3824-4014	sentence	denotes	Furthermore, comparison of this animal model with human MSUD has shown some differences in the pathology of the disease [1], making this animal a less desirable model for the human disease.
T4076	3825-3836	RB	denotes	Furthermore
T4077	3890-3895	VBN	denotes	shown
T4078	3836-3838	,	denotes	,
T4079	3838-3848	NN	denotes	comparison
T4080	3849-3851	IN	denotes	of
T4081	3852-3856	DT	denotes	this
T4082	3864-3869	NN	denotes	model
T4083	3857-3863	NN	denotes	animal
T4084	3870-3874	IN	denotes	with
T4085	3875-3880	JJ	denotes	human
T4086	3881-3885	NN	denotes	MSUD
T4087	3886-3889	VBZ	denotes	has
T4088	3896-3900	DT	denotes	some
T4089	3901-3912	NNS	denotes	differences
T4090	3913-3915	IN	denotes	in
T4091	3916-3919	DT	denotes	the
T4092	3920-3929	NN	denotes	pathology
T4093	3930-3932	IN	denotes	of
T4094	3933-3936	DT	denotes	the
T4095	3937-3944	NN	denotes	disease
T4096	3945-3946	-LRB-	denotes	[
T4097	3946-3947	CD	denotes	1
T4098	3947-3948	-RRB-	denotes	]
T4099	3948-3950	,	denotes	,
T4100	3950-3956	VBG	denotes	making
T4101	3957-3961	DT	denotes	this
T4102	3962-3968	NN	denotes	animal
T4103	3986-3991	NN	denotes	model
T4104	3969-3970	DT	denotes	a
T4105	3971-3975	RBR	denotes	less
T4106	3976-3985	JJ	denotes	desirable
T4107	3992-3995	IN	denotes	for
T4108	3996-3999	DT	denotes	the
T4109	4006-4013	NN	denotes	disease
T4110	4000-4005	JJ	denotes	human
T4111	4013-4014	.	denotes	.
T4112	4014-4141	sentence	denotes	Recently, a N-ethyl-N-nitrosourea (ENU)-induced mutant mouse that phenotypically resembles human MSUD has been described [20].
T4113	4015-4023	RB	denotes	Recently
T4114	4126-4135	VBN	denotes	described
T4115	4023-4025	,	denotes	,
T4116	4025-4026	DT	denotes	a
T4117	4037-4048	NN	denotes	nitrosourea
T4118	4027-4028	NN	denotes	N
T4119	4029-4034	NN	denotes	ethyl
T4120	4028-4029	HYPH	denotes	-
T4121	4034-4035	HYPH	denotes	-
T4122	4035-4036	NN	denotes	N
T4123	4036-4037	HYPH	denotes	-
T4124	4055-4062	VBN	denotes	induced
T4125	4049-4050	-LRB-	denotes	(
T4126	4050-4053	NN	denotes	ENU
T4127	4053-4054	-RRB-	denotes	)
T4128	4054-4055	HYPH	denotes	-
T4129	4070-4075	NN	denotes	mouse
T4130	4063-4069	NN	denotes	mutant
T4131	4076-4080	WDT	denotes	that
T4132	4096-4105	VBZ	denotes	resembles
T4133	4081-4095	RB	denotes	phenotypically
T4134	4106-4111	JJ	denotes	human
T4135	4112-4116	NN	denotes	MSUD
T4136	4117-4120	VBZ	denotes	has
T4137	4121-4125	VBN	denotes	been
T4138	4136-4137	-LRB-	denotes	[
T4139	4137-4139	CD	denotes	20
T4140	4139-4140	-RRB-	denotes	]
T4141	4140-4141	.	denotes	.
T4142	4141-4310	sentence	denotes	However, the mutation in this model disrupts a splice site in the mitochondrial branched-chain aminotransferase (BCAT) gene, not in BCKDH, the deficient enzyme in MSUD.
T4143	4142-4149	RB	denotes	However
T4144	4178-4186	VBZ	denotes	disrupts
T4145	4149-4151	,	denotes	,
T4146	4151-4154	DT	denotes	the
T4147	4155-4163	NN	denotes	mutation
T4148	4164-4166	IN	denotes	in
T4149	4167-4171	DT	denotes	this
T4150	4172-4177	NN	denotes	model
T4151	4187-4188	DT	denotes	a
T4152	4196-4200	NN	denotes	site
T4153	4189-4195	NN	denotes	splice
T4154	4201-4203	IN	denotes	in
T4155	4204-4207	DT	denotes	the
T4156	4237-4253	NN	denotes	aminotransferase
T4157	4208-4221	JJ	denotes	mitochondrial
T4158	4222-4230	VBN	denotes	branched
T4159	4231-4236	NN	denotes	chain
T4160	4230-4231	HYPH	denotes	-
T4161	4261-4265	NN	denotes	gene
T4162	4254-4255	-LRB-	denotes	(
T4163	4255-4259	NN	denotes	BCAT
T4164	4259-4260	-RRB-	denotes	)
T4165	4265-4267	,	denotes	,
T4166	4267-4270	RB	denotes	not
T4167	4271-4273	IN	denotes	in
T4168	4274-4279	NN	denotes	BCKDH
T4169	4279-4281	,	denotes	,
T4170	4281-4284	DT	denotes	the
T4171	4295-4301	NN	denotes	enzyme
T4172	4285-4294	JJ	denotes	deficient
T4173	4302-4304	IN	denotes	in
T4174	4305-4309	NN	denotes	MSUD
T4175	4309-4310	.	denotes	.
T4176	4310-4428	sentence	denotes	Because the mutation is not in BCKDH, the validity of this mutant mouse line for modeling human MSUD is questionable.
T4177	4311-4318	IN	denotes	Because
T4178	4332-4334	VBZ	denotes	is
T4179	4319-4322	DT	denotes	the
T4180	4323-4331	NN	denotes	mutation
T4181	4412-4414	VBZ	denotes	is
T4182	4335-4338	RB	denotes	not
T4183	4339-4341	IN	denotes	in
T4184	4342-4347	NN	denotes	BCKDH
T4185	4347-4349	,	denotes	,
T4186	4349-4352	DT	denotes	the
T4187	4353-4361	NN	denotes	validity
T4188	4362-4364	IN	denotes	of
T4189	4365-4369	DT	denotes	this
T4190	4383-4387	NN	denotes	line
T4191	4370-4376	NN	denotes	mutant
T4192	4377-4382	NN	denotes	mouse
T4193	4388-4391	IN	denotes	for
T4194	4392-4400	VBG	denotes	modeling
T4195	4407-4411	NN	denotes	MSUD
T4196	4401-4406	JJ	denotes	human
T4197	4415-4427	JJ	denotes	questionable
T4198	4427-4428	.	denotes	.
T4199	4428-4615	sentence	denotes	The objective of the present study was to create genetically engineered murine models of MSUD that mimic the pathology of the classic and intermediate variant forms of the human disease.
T4200	4429-4432	DT	denotes	The
T4201	4433-4442	NN	denotes	objective
T4202	4464-4467	VBD	denotes	was
T4203	4443-4445	IN	denotes	of
T4204	4446-4449	DT	denotes	the
T4205	4458-4463	NN	denotes	study
T4206	4450-4457	JJ	denotes	present
T4207	4468-4470	TO	denotes	to
T4208	4471-4477	VB	denotes	create
T4209	4478-4489	RB	denotes	genetically
T4210	4490-4500	VBN	denotes	engineered
T4211	4508-4514	NNS	denotes	models
T4212	4501-4507	JJ	denotes	murine
T4213	4515-4517	IN	denotes	of
T4214	4518-4522	NN	denotes	MSUD
T4215	4523-4527	WDT	denotes	that
T4216	4528-4533	VBP	denotes	mimic
T4217	4534-4537	DT	denotes	the
T4218	4538-4547	NN	denotes	pathology
T4219	4548-4550	IN	denotes	of
T4220	4551-4554	DT	denotes	the
T4221	4588-4593	NNS	denotes	forms
T4222	4555-4562	JJ	denotes	classic
T4223	4563-4566	CC	denotes	and
T4224	4567-4579	JJ	denotes	intermediate
T4225	4580-4587	JJ	denotes	variant
T4226	4594-4596	IN	denotes	of
T4227	4597-4600	DT	denotes	the
T4228	4607-4614	NN	denotes	disease
T4229	4601-4606	JJ	denotes	human
T4230	4614-4615	.	denotes	.
T4231	4615-4755	sentence	denotes	The classic model was created by targeted inactivation of the E2 subunit of BCKDH by homologous recombination in embryonic stem (ES) cells.
T4232	4616-4619	DT	denotes	The
T4233	4628-4633	NN	denotes	model
T4234	4620-4627	JJ	denotes	classic
T4235	4638-4645	VBN	denotes	created
T4236	4634-4637	VBD	denotes	was
T4237	4646-4648	IN	denotes	by
T4238	4649-4657	VBN	denotes	targeted
T4239	4658-4670	NN	denotes	inactivation
T4240	4671-4673	IN	denotes	of
T4241	4674-4677	DT	denotes	the
T4242	4681-4688	NN	denotes	subunit
T4243	4678-4680	NN	denotes	E2
T4244	4689-4691	IN	denotes	of
T4245	4692-4697	NN	denotes	BCKDH
T4246	4698-4700	IN	denotes	by
T4247	4701-4711	JJ	denotes	homologous
T4248	4712-4725	NN	denotes	recombination
T4249	4726-4728	IN	denotes	in
T4250	4729-4738	JJ	denotes	embryonic
T4251	4745-4747	NN	denotes	ES
T4252	4739-4743	NN	denotes	stem
T4253	4744-4745	-LRB-	denotes	(
T4254	4749-4754	NNS	denotes	cells
T4255	4747-4748	-RRB-	denotes	)
T4256	4754-4755	.	denotes	.
T4257	4755-4852	sentence	denotes	The model of intermediate MSUD was created by partial transgenic rescue of the E2 gene knockout.
T4258	4756-4759	DT	denotes	The
T4259	4760-4765	NN	denotes	model
T4260	4791-4798	VBN	denotes	created
T4261	4766-4768	IN	denotes	of
T4262	4769-4781	JJ	denotes	intermediate
T4263	4782-4786	NN	denotes	MSUD
T4264	4787-4790	VBD	denotes	was
T4265	4799-4801	IN	denotes	by
T4266	4802-4809	JJ	denotes	partial
T4267	4821-4827	NN	denotes	rescue
T4268	4810-4820	JJ	denotes	transgenic
T4269	4828-4830	IN	denotes	of
T4270	4831-4834	DT	denotes	the
T4271	4843-4851	NN	denotes	knockout
T4272	4835-4837	NN	denotes	E2
T4273	4838-4842	NN	denotes	gene
T4274	4851-4852	.	denotes	.
T4275	4852-4942	sentence	denotes	This report describes the generation and characterization of these murine models of MSUD.
T4276	4853-4857	DT	denotes	This
T4277	4858-4864	NN	denotes	report
T4278	4865-4874	VBZ	denotes	describes
T4279	4875-4878	DT	denotes	the
T4280	4879-4889	NN	denotes	generation
T4281	4890-4893	CC	denotes	and
T4282	4894-4910	NN	denotes	characterization
T4283	4911-4913	IN	denotes	of
T4284	4914-4919	DT	denotes	these
T4285	4927-4933	NNS	denotes	models
T4286	4920-4926	JJ	denotes	murine
T4287	4934-4936	IN	denotes	of
T4288	4937-4941	NN	denotes	MSUD
T4289	4941-4942	.	denotes	.
T4290	4942-5079	sentence	denotes	These models will allow for the development of novel treatment approaches, such as gene or stem cell therapies, to ultimately cure MSUD.
T4291	4943-4948	DT	denotes	These
T4292	4949-4955	NNS	denotes	models
T4293	4961-4966	VB	denotes	allow
T4294	4956-4960	MD	denotes	will
T4295	4967-4970	IN	denotes	for
T4296	4971-4974	DT	denotes	the
T4297	4975-4986	NN	denotes	development
T4298	4987-4989	IN	denotes	of
T4299	4990-4995	JJ	denotes	novel
T4300	5006-5016	NNS	denotes	approaches
T4301	4996-5005	NN	denotes	treatment
T4302	5016-5018	,	denotes	,
T4303	5018-5022	JJ	denotes	such
T4304	5023-5025	IN	denotes	as
T4305	5026-5030	NN	denotes	gene
T4306	5044-5053	NNS	denotes	therapies
T4307	5031-5033	CC	denotes	or
T4308	5034-5038	NN	denotes	stem
T4309	5039-5043	NN	denotes	cell
T4310	5053-5055	,	denotes	,
T4311	5055-5057	TO	denotes	to
T4312	5069-5073	VB	denotes	cure
T4313	5058-5068	RB	denotes	ultimately
T4314	5074-5078	NN	denotes	MSUD
T4315	5078-5079	.	denotes	.
T4359	5089-5092	DT	denotes	All
T4360	5093-5100	NNS	denotes	studies
T4361	5124-5132	VBN	denotes	reviewed
T4362	5101-5110	VBG	denotes	involving
T4363	5111-5118	NNS	denotes	animals
T4364	5119-5123	VBD	denotes	were
T4365	5133-5136	CC	denotes	and
T4366	5137-5145	VBN	denotes	approved
T4367	5146-5148	IN	denotes	by
T4368	5149-5152	DT	denotes	the
T4369	5153-5163	NNP	denotes	University
T4370	5164-5166	IN	denotes	of
T4371	5167-5177	NNP	denotes	Pittsburgh
T4372	5214-5223	NNP	denotes	Committee
T4373	5177-5179	POS	denotes	's
T4374	5180-5193	NNP	denotes	Institutional
T4375	5194-5200	NNP	denotes	Animal
T4376	5201-5205	NNP	denotes	Care
T4377	5206-5209	CC	denotes	and
T4378	5210-5213	NNP	denotes	Use
T4379	5223-5224	.	denotes	.
T5027	5226-5230	NN	denotes	Gene
T5028	5231-5239	NN	denotes	knockout
T5029	5240-5250	NN	denotes	production
T5030	5250-5476	sentence	denotes	A genomic DNA subclone of Strain 129/SvJ DNA that contained a portion of Exons 4 and 5 of the E2 gene and flanking DNA was obtained from a P1 phage library from Genome Systems, Inc., (St. Louis, MO; '3-Hit Mouse ES Library').
T5031	5251-5252	DT	denotes	A
T5032	5265-5273	NN	denotes	subclone
T5033	5253-5260	JJ	denotes	genomic
T5034	5261-5264	NN	denotes	DNA
T5035	5374-5382	VBN	denotes	obtained
T5036	5274-5276	IN	denotes	of
T5037	5277-5283	NN	denotes	Strain
T5038	5292-5295	NN	denotes	DNA
T5039	5284-5287	CD	denotes	129
T5040	5288-5291	NN	denotes	SvJ
T5041	5287-5288	HYPH	denotes	/
T5042	5296-5300	WDT	denotes	that
T5043	5301-5310	VBD	denotes	contained
T5044	5311-5312	DT	denotes	a
T5045	5313-5320	NN	denotes	portion
T5046	5321-5323	IN	denotes	of
T5047	5324-5329	NNS	denotes	Exons
T5048	5330-5331	CD	denotes	4
T5049	5332-5335	CC	denotes	and
T5050	5336-5337	CD	denotes	5
T5051	5338-5340	IN	denotes	of
T5052	5341-5344	DT	denotes	the
T5053	5348-5352	NN	denotes	gene
T5054	5345-5347	NN	denotes	E2
T5055	5353-5356	CC	denotes	and
T5056	5357-5365	NN	denotes	flanking
T5057	5366-5369	NN	denotes	DNA
T5058	5370-5373	VBD	denotes	was
T5059	5383-5387	IN	denotes	from
T5060	5388-5389	DT	denotes	a
T5061	5399-5406	NN	denotes	library
T5062	5390-5392	NN	denotes	P1
T5063	5393-5398	NN	denotes	phage
T5064	5407-5411	IN	denotes	from
T5065	5412-5418	NNP	denotes	Genome
T5066	5428-5432	NNP	denotes	Inc.
T5067	5419-5426	NNP	denotes	Systems
T5068	5426-5428	,	denotes	,
T5069	5432-5434	,	denotes	,
T5070	5434-5435	-LRB-	denotes	(
T5071	5466-5473	NNP	denotes	Library
T5072	5435-5438	NNP	denotes	St.
T5073	5439-5444	NNP	denotes	Louis
T5074	5444-5446	,	denotes	,
T5075	5446-5448	NNP	denotes	MO
T5076	5448-5449	:	denotes	;
T5077	5450-5451	SYM	denotes	'
T5078	5451-5452	CD	denotes	3
T5079	5453-5456	NN	denotes	Hit
T5080	5452-5453	HYPH	denotes	-
T5081	5457-5462	NNP	denotes	Mouse
T5082	5463-5465	NNP	denotes	ES
T5083	5473-5474	POS	denotes	'
T5084	5474-5475	-RRB-	denotes	)
T5085	5475-5476	.	denotes	.
T5086	5476-5716	sentence	denotes	A positive/negative replacement type gene targeting vector [21] was created by replacing a 1.67 kb EcoRV-Smal fragment that included a portion of Exon 4 and all of Exon 5 with the PGKneo marker gene (See Fig. 1A) from the pPNT vector [22].
T5087	5477-5478	DT	denotes	A
T5088	5529-5535	NN	denotes	vector
T5089	5479-5487	JJ	denotes	positive
T5090	5488-5496	JJ	denotes	negative
T5091	5487-5488	HYPH	denotes	/
T5092	5497-5508	NN	denotes	replacement
T5093	5509-5513	NN	denotes	type
T5094	5514-5518	NN	denotes	gene
T5095	5519-5528	NN	denotes	targeting
T5096	5545-5552	VBN	denotes	created
T5097	5536-5537	-LRB-	denotes	[
T5098	5537-5539	CD	denotes	21
T5099	5539-5540	-RRB-	denotes	]
T5100	5541-5544	VBD	denotes	was
T5101	5553-5555	IN	denotes	by
T5102	5556-5565	VBG	denotes	replacing
T5103	5566-5567	DT	denotes	a
T5104	5587-5595	NN	denotes	fragment
T5105	5568-5572	CD	denotes	1.67
T5106	5573-5575	NN	denotes	kb
T5107	5576-5581	NN	denotes	EcoRV
T5108	5582-5586	NN	denotes	Smal
T5109	5581-5582	HYPH	denotes	-
T5110	5596-5600	WDT	denotes	that
T5111	5601-5609	VBD	denotes	included
T5112	5610-5611	DT	denotes	a
T5113	5612-5619	NN	denotes	portion
T5114	5620-5622	IN	denotes	of
T5115	5623-5627	NN	denotes	Exon
T5116	5628-5629	CD	denotes	4
T5117	5630-5633	CC	denotes	and
T5118	5634-5637	DT	denotes	all
T5119	5638-5640	IN	denotes	of
T5120	5641-5645	NN	denotes	Exon
T5121	5646-5647	CD	denotes	5
T5122	5648-5652	IN	denotes	with
T5123	5653-5656	DT	denotes	the
T5124	5671-5675	NN	denotes	gene
T5125	5657-5663	NN	denotes	PGKneo
T5126	5664-5670	NN	denotes	marker
T5127	5676-5677	-LRB-	denotes	(
T5128	5677-5680	VB	denotes	See
T5129	5681-5685	NN	denotes	Fig.
T5130	5686-5688	NN	denotes	1A
T5131	5688-5689	-RRB-	denotes	)
T5132	5690-5694	IN	denotes	from
T5133	5695-5698	DT	denotes	the
T5134	5704-5710	NN	denotes	vector
T5135	5699-5703	NN	denotes	pPNT
T5136	5711-5712	-LRB-	denotes	[
T5137	5712-5714	CD	denotes	22
T5138	5714-5715	-RRB-	denotes	]
T5139	5715-5716	.	denotes	.
T5140	5716-5850	sentence	denotes	The targeting construct was linearized with NotI and electroporated into R1 ES cells [23] under conditions described previously [24].
T5141	5717-5720	DT	denotes	The
T5142	5731-5740	NN	denotes	construct
T5143	5721-5730	NN	denotes	targeting
T5144	5745-5755	VBN	denotes	linearized
T5145	5741-5744	VBD	denotes	was
T5146	5756-5760	IN	denotes	with
T5147	5761-5765	NN	denotes	NotI
T5148	5766-5769	CC	denotes	and
T5149	5770-5784	VBN	denotes	electroporated
T5150	5785-5789	IN	denotes	into
T5151	5790-5792	NN	denotes	R1
T5152	5796-5801	NNS	denotes	cells
T5153	5793-5795	NN	denotes	ES
T5154	5802-5803	-LRB-	denotes	[
T5155	5803-5805	CD	denotes	23
T5156	5805-5806	-RRB-	denotes	]
T5157	5807-5812	IN	denotes	under
T5158	5813-5823	NNS	denotes	conditions
T5159	5824-5833	VBN	denotes	described
T5160	5834-5844	RB	denotes	previously
T5161	5845-5846	-LRB-	denotes	[
T5162	5846-5848	CD	denotes	24
T5163	5848-5849	-RRB-	denotes	]
T5164	5849-5850	.	denotes	.
T5165	5850-5992	sentence	denotes	ES cells were selected with G418 (300 μg/ml; Life Technologies Inc., Gaithersburg, MD) and gancyclovir (2 μM; gift of Syntex, Palo Alto, CA).
T5166	5851-5853	NN	denotes	ES
T5167	5854-5859	NNS	denotes	cells
T5168	5865-5873	VBN	denotes	selected
T5169	5860-5864	VBD	denotes	were
T5170	5874-5878	IN	denotes	with
T5171	5879-5883	NN	denotes	G418
T5172	5884-5885	-LRB-	denotes	(
T5173	5914-5918	NNP	denotes	Inc.
T5174	5885-5888	CD	denotes	300
T5175	5889-5891	NN	denotes	μg
T5176	5891-5892	SYM	denotes	/
T5177	5892-5894	NN	denotes	ml
T5178	5894-5895	:	denotes	;
T5179	5896-5900	NNP	denotes	Life
T5180	5901-5913	NNP	denotes	Technologies
T5181	5918-5920	,	denotes	,
T5182	5920-5932	NNP	denotes	Gaithersburg
T5183	5932-5934	,	denotes	,
T5184	5934-5936	NNP	denotes	MD
T5185	5936-5937	-RRB-	denotes	)
T5186	5938-5941	CC	denotes	and
T5187	5942-5953	NN	denotes	gancyclovir
T5188	5954-5955	-LRB-	denotes	(
T5189	5955-5956	CD	denotes	2
T5190	5957-5959	NN	denotes	μM
T5191	5959-5960	:	denotes	;
T5192	5961-5965	NN	denotes	gift
T5193	5966-5968	IN	denotes	of
T5194	5969-5975	NNP	denotes	Syntex
T5195	5975-5977	,	denotes	,
T5196	5977-5981	NNP	denotes	Palo
T5197	5982-5986	NNP	denotes	Alto
T5198	5986-5988	,	denotes	,
T5199	5988-5990	NNP	denotes	CA
T5200	5990-5991	-RRB-	denotes	)
T5201	5991-5992	.	denotes	.
T5202	5992-6105	sentence	denotes	Doubly resistant clones were screened for gene targeting by Southern blot analysis of BglI digested genomic DNA.
T5203	5993-5999	RB	denotes	Doubly
T5204	6000-6009	JJ	denotes	resistant
T5205	6010-6016	NNS	denotes	clones
T5206	6022-6030	VBN	denotes	screened
T5207	6017-6021	VBD	denotes	were
T5208	6031-6034	IN	denotes	for
T5209	6035-6039	NN	denotes	gene
T5210	6040-6049	NN	denotes	targeting
T5211	6050-6052	IN	denotes	by
T5212	6053-6061	NNP	denotes	Southern
T5213	6062-6066	NN	denotes	blot
T5214	6067-6075	NN	denotes	analysis
T5215	6076-6078	IN	denotes	of
T5216	6079-6083	NN	denotes	BglI
T5217	6101-6104	NN	denotes	DNA
T5218	6084-6092	VBN	denotes	digested
T5219	6093-6100	JJ	denotes	genomic
T5220	6104-6105	.	denotes	.
T5221	6105-6208	sentence	denotes	Blots were hybridized with an Exon 6 specific probe that was external to the gene targeting construct.
T5222	6106-6111	NNS	denotes	Blots
T5223	6117-6127	VBN	denotes	hybridized
T5224	6112-6116	VBD	denotes	were
T5225	6128-6132	IN	denotes	with
T5226	6133-6135	DT	denotes	an
T5227	6152-6157	NN	denotes	probe
T5228	6136-6140	NN	denotes	Exon
T5229	6143-6151	JJ	denotes	specific
T5230	6141-6142	CD	denotes	6
T5231	6158-6162	WDT	denotes	that
T5232	6163-6166	VBD	denotes	was
T5233	6167-6175	JJ	denotes	external
T5234	6176-6178	IN	denotes	to
T5235	6179-6182	DT	denotes	the
T5236	6198-6207	NN	denotes	construct
T5237	6183-6187	NN	denotes	gene
T5238	6188-6197	NN	denotes	targeting
T5239	6207-6208	.	denotes	.
T5240	6208-6328	sentence	denotes	Correctly targeted ES cells were injected into C57BL/6J blastocysts to produce chimeric mice using standard procedures.
T5241	6209-6218	RB	denotes	Correctly
T5242	6219-6227	VBN	denotes	targeted
T5243	6231-6236	NNS	denotes	cells
T5244	6228-6230	NN	denotes	ES
T5245	6242-6250	VBN	denotes	injected
T5246	6237-6241	VBD	denotes	were
T5247	6251-6255	IN	denotes	into
T5248	6256-6261	NN	denotes	C57BL
T5249	6262-6264	NN	denotes	6J
T5250	6261-6262	HYPH	denotes	/
T5251	6265-6276	NNS	denotes	blastocysts
T5252	6277-6279	TO	denotes	to
T5253	6280-6287	VB	denotes	produce
T5254	6288-6296	JJ	denotes	chimeric
T5255	6297-6301	NNS	denotes	mice
T5256	6302-6307	VBG	denotes	using
T5257	6308-6316	JJ	denotes	standard
T5258	6317-6327	NNS	denotes	procedures
T5259	6327-6328	.	denotes	.
T5260	6328-6485	sentence	denotes	Heterozygous offspring from germline competent chimeras were intercrossed to produce wild type (+/+), heterozygous (+/-) and homozygous knockout (-/-) mice.
T5261	6329-6341	JJ	denotes	Heterozygous
T5262	6342-6351	NN	denotes	offspring
T5263	6390-6402	VBN	denotes	intercrossed
T5264	6352-6356	IN	denotes	from
T5265	6357-6365	NN	denotes	germline
T5266	6366-6375	JJ	denotes	competent
T5267	6376-6384	NNS	denotes	chimeras
T5268	6385-6389	VBD	denotes	were
T5269	6403-6405	TO	denotes	to
T5270	6406-6413	VB	denotes	produce
T5271	6414-6418	JJ	denotes	wild
T5272	6419-6423	NN	denotes	type
T5273	6465-6473	NN	denotes	knockout
T5274	6424-6425	-LRB-	denotes	(
T5275	6427-6428	SYM	denotes	+
T5276	6425-6426	SYM	denotes	+
T5277	6426-6427	HYPH	denotes	/
T5278	6428-6429	-RRB-	denotes	)
T5279	6429-6431	,	denotes	,
T5280	6431-6443	JJ	denotes	heterozygous
T5281	6444-6445	-LRB-	denotes	(
T5282	6447-6448	SYM	denotes	-
T5283	6445-6446	SYM	denotes	+
T5284	6446-6447	HYPH	denotes	/
T5285	6448-6449	-RRB-	denotes	)
T5286	6450-6453	CC	denotes	and
T5287	6454-6464	JJ	denotes	homozygous
T5288	6480-6484	NNS	denotes	mice
T5289	6474-6475	-LRB-	denotes	(
T5290	6477-6478	SYM	denotes	-
T5291	6475-6476	SYM	denotes	-
T5292	6476-6477	HYPH	denotes	/
T5293	6478-6479	-RRB-	denotes	)
T5294	6484-6485	.	denotes	.
T5295	6485-6535	sentence	denotes	At all generations, +/- breeding pairs were used.
T5296	6486-6488	IN	denotes	At
T5297	6530-6534	VBN	denotes	used
T5298	6489-6492	DT	denotes	all
T5299	6493-6504	NNS	denotes	generations
T5300	6504-6506	,	denotes	,
T5301	6506-6507	SYM	denotes	+
T5302	6508-6509	SYM	denotes	-
T5303	6507-6508	HYPH	denotes	/
T5304	6519-6524	NNS	denotes	pairs
T5305	6510-6518	VBG	denotes	breeding
T5306	6525-6529	VBD	denotes	were
T5307	6534-6535	.	denotes	.
T5308	6535-6606	sentence	denotes	Results presented here are from mice derived from the F2+ generations.
T5309	6536-6543	NNS	denotes	Results
T5310	6559-6562	VBP	denotes	are
T5311	6544-6553	VBN	denotes	presented
T5312	6554-6558	RB	denotes	here
T5313	6563-6567	IN	denotes	from
T5314	6568-6572	NNS	denotes	mice
T5315	6573-6580	VBN	denotes	derived
T5316	6581-6585	IN	denotes	from
T5317	6586-6589	DT	denotes	the
T5318	6594-6605	NNS	denotes	generations
T5319	6590-6592	NN	denotes	F2
T5320	6592-6593	SYM	denotes	+
T5321	6605-6606	.	denotes	.
T5322	6606-6682	sentence	denotes	All animals were of a mixed C57BL/6J × Strain 129Sv/SvJ genetic background.
T5323	6607-6610	DT	denotes	All
T5324	6611-6618	NNS	denotes	animals
T5325	6619-6623	VBD	denotes	were
T5326	6624-6626	IN	denotes	of
T5327	6627-6628	DT	denotes	a
T5328	6671-6681	NN	denotes	background
T5329	6629-6634	VBN	denotes	mixed
T5330	6635-6640	NN	denotes	C57BL
T5331	6641-6643	NN	denotes	6J
T5332	6640-6641	HYPH	denotes	/
T5333	6644-6645	SYM	denotes	×
T5334	6646-6652	NN	denotes	Strain
T5335	6659-6662	NN	denotes	SvJ
T5336	6653-6658	NN	denotes	129Sv
T5337	6658-6659	HYPH	denotes	/
T5338	6663-6670	JJ	denotes	genetic
T5339	6681-6682	.	denotes	.
T5872	8164-8174	NN	denotes	Production
T5873	8175-8177	IN	denotes	of
T5874	8178-8188	JJ	denotes	transgenic
T5875	8189-8193	NNS	denotes	mice
T5876	8193-8280	sentence	denotes	Standard molecular techniques were used to assemble the transgenic construct, pTRE-E2.
T5877	8194-8202	JJ	denotes	Standard
T5878	8213-8223	NNS	denotes	techniques
T5879	8203-8212	JJ	denotes	molecular
T5880	8229-8233	VBN	denotes	used
T5881	8224-8228	VBD	denotes	were
T5882	8234-8236	TO	denotes	to
T5883	8237-8245	VB	denotes	assemble
T5884	8246-8249	DT	denotes	the
T5885	8261-8270	NN	denotes	construct
T5886	8250-8260	JJ	denotes	transgenic
T5887	8270-8272	,	denotes	,
T5888	8272-8276	NN	denotes	pTRE
T5889	8277-8279	NN	denotes	E2
T5890	8276-8277	HYPH	denotes	-
T5891	8279-8280	.	denotes	.
T5892	8280-8904	sentence	denotes	This transgene contains the tetracycline responsive hCMV*-1 promoter [consisting of the tetracycline responsive element (TRE) and a minimal hCMV promoter] [25] from pTRE2 (Clontech Inc., Mt. View, CA), a chimeric intron from pCI (Promega) to increase message stability and expression [26,27], a Kozak consensus sequence at the initiation codon to optimize translation [28], the human E2 cDNA which has been modified to contain a 4× alanine linker followed by a c-myc epitope tag at the carboxy terminus to facilitate detection, and an SV40 late polyadenylation sequence from pCI for enhanced mRNA stability and translation.
T5893	8281-8285	DT	denotes	This
T5894	8286-8295	NN	denotes	transgene
T5895	8296-8304	VBZ	denotes	contains
T5896	8305-8308	DT	denotes	the
T5897	8341-8349	NN	denotes	promoter
T5898	8309-8321	NN	denotes	tetracycline
T5899	8322-8332	JJ	denotes	responsive
T5900	8333-8337	NN	denotes	hCMV
T5901	8337-8338	SYM	denotes	*
T5902	8338-8339	HYPH	denotes	-
T5903	8339-8340	CD	denotes	1
T5904	8350-8351	-LRB-	denotes	[
T5905	8351-8361	VBG	denotes	consisting
T5906	8362-8364	IN	denotes	of
T5907	8365-8368	DT	denotes	the
T5908	8393-8400	NN	denotes	element
T5909	8369-8381	NN	denotes	tetracycline
T5910	8382-8392	JJ	denotes	responsive
T5911	8401-8402	-LRB-	denotes	(
T5912	8402-8405	NN	denotes	TRE
T5913	8405-8406	-RRB-	denotes	)
T5914	8407-8410	CC	denotes	and
T5915	8411-8412	DT	denotes	a
T5916	8426-8434	NN	denotes	promoter
T5917	8413-8420	JJ	denotes	minimal
T5918	8421-8425	NN	denotes	hCMV
T5919	8434-8435	-RRB-	denotes	]
T5920	8436-8437	-LRB-	denotes	[
T5921	8437-8439	CD	denotes	25
T5922	8439-8440	-RRB-	denotes	]
T5923	8441-8445	IN	denotes	from
T5924	8446-8451	NN	denotes	pTRE2
T5925	8452-8453	-LRB-	denotes	(
T5926	8462-8466	NNP	denotes	Inc.
T5927	8453-8461	NNP	denotes	Clontech
T5928	8466-8468	,	denotes	,
T5929	8468-8471	NNP	denotes	Mt.
T5930	8472-8476	NNP	denotes	View
T5931	8476-8478	,	denotes	,
T5932	8478-8480	NNP	denotes	CA
T5933	8480-8481	-RRB-	denotes	)
T5934	8481-8483	,	denotes	,
T5935	8483-8484	DT	denotes	a
T5936	8494-8500	NN	denotes	intron
T5937	8485-8493	JJ	denotes	chimeric
T5938	8501-8505	IN	denotes	from
T5939	8506-8509	NN	denotes	pCI
T5940	8510-8511	-LRB-	denotes	(
T5941	8511-8518	NNP	denotes	Promega
T5942	8518-8519	-RRB-	denotes	)
T5943	8520-8522	TO	denotes	to
T5944	8523-8531	VB	denotes	increase
T5945	8532-8539	NN	denotes	message
T5946	8540-8549	NN	denotes	stability
T5947	8550-8553	CC	denotes	and
T5948	8554-8564	NN	denotes	expression
T5949	8565-8566	-LRB-	denotes	[
T5950	8569-8571	CD	denotes	27
T5951	8566-8568	CD	denotes	26
T5952	8568-8569	,	denotes	,
T5953	8571-8572	-RRB-	denotes	]
T5954	8572-8574	,	denotes	,
T5955	8574-8575	DT	denotes	a
T5956	8592-8600	NN	denotes	sequence
T5957	8576-8581	NN	denotes	Kozak
T5958	8582-8591	NN	denotes	consensus
T5959	8601-8603	IN	denotes	at
T5960	8604-8607	DT	denotes	the
T5961	8619-8624	NN	denotes	codon
T5962	8608-8618	NN	denotes	initiation
T5963	8625-8627	TO	denotes	to
T5964	8628-8636	VB	denotes	optimize
T5965	8637-8648	NN	denotes	translation
T5966	8649-8650	-LRB-	denotes	[
T5967	8650-8652	CD	denotes	28
T5968	8652-8653	-RRB-	denotes	]
T5969	8653-8655	,	denotes	,
T5970	8655-8658	DT	denotes	the
T5971	8668-8672	NN	denotes	cDNA
T5972	8659-8664	JJ	denotes	human
T5973	8665-8667	NN	denotes	E2
T5974	8673-8678	WDT	denotes	which
T5975	8688-8696	VBN	denotes	modified
T5976	8679-8682	VBZ	denotes	has
T5977	8683-8687	VBN	denotes	been
T5978	8697-8699	TO	denotes	to
T5979	8700-8707	VB	denotes	contain
T5980	8708-8709	DT	denotes	a
T5981	8721-8727	NN	denotes	linker
T5982	8710-8711	CD	denotes	4
T5983	8711-8712	SYM	denotes	×
T5984	8713-8720	NN	denotes	alanine
T5985	8728-8736	VBN	denotes	followed
T5986	8737-8739	IN	denotes	by
T5987	8740-8741	DT	denotes	a
T5988	8756-8759	NN	denotes	tag
T5989	8742-8743	NN	denotes	c
T5990	8744-8747	NN	denotes	myc
T5991	8743-8744	HYPH	denotes	-
T5992	8748-8755	NN	denotes	epitope
T5993	8760-8762	IN	denotes	at
T5994	8763-8766	DT	denotes	the
T5995	8775-8783	NN	denotes	terminus
T5996	8767-8774	NN	denotes	carboxy
T5997	8784-8786	TO	denotes	to
T5998	8787-8797	VB	denotes	facilitate
T5999	8798-8807	NN	denotes	detection
T6000	8807-8809	,	denotes	,
T6001	8809-8812	CC	denotes	and
T6002	8813-8815	DT	denotes	an
T6003	8842-8850	NN	denotes	sequence
T6004	8816-8820	NN	denotes	SV40
T6005	8821-8825	JJ	denotes	late
T6006	8826-8841	NN	denotes	polyadenylation
T6007	8851-8855	IN	denotes	from
T6008	8856-8859	NN	denotes	pCI
T6009	8860-8863	IN	denotes	for
T6010	8864-8872	VBN	denotes	enhanced
T6011	8878-8887	NN	denotes	stability
T6012	8873-8877	NN	denotes	mRNA
T6013	8888-8891	CC	denotes	and
T6014	8892-8903	NN	denotes	translation
T6015	8903-8904	.	denotes	.
T6016	8904-9192	sentence	denotes	The 2.48 kb TRE-E2 transgene was purified from vector sequences following digestion with XhoI and BamHI and injected into C57BL/6J or C57BL/6J × Strain 129SvEv mouse embryos at the transgenic core facilities of the University of Pittsburgh and the University of Cincinnati, respectively.
T6017	8905-8908	DT	denotes	The
T6018	8924-8933	NN	denotes	transgene
T6019	8909-8913	CD	denotes	2.48
T6020	8914-8916	NN	denotes	kb
T6021	8917-8920	NN	denotes	TRE
T6022	8921-8923	NN	denotes	E2
T6023	8920-8921	HYPH	denotes	-
T6024	8938-8946	VBN	denotes	purified
T6025	8934-8937	VBD	denotes	was
T6026	8947-8951	IN	denotes	from
T6027	8952-8958	NN	denotes	vector
T6028	8959-8968	NNS	denotes	sequences
T6029	8969-8978	VBG	denotes	following
T6030	8979-8988	NN	denotes	digestion
T6031	8989-8993	IN	denotes	with
T6032	8994-8998	NN	denotes	XhoI
T6033	8999-9002	CC	denotes	and
T6034	9003-9008	NN	denotes	BamHI
T6035	9009-9012	CC	denotes	and
T6036	9013-9021	VBN	denotes	injected
T6037	9022-9026	IN	denotes	into
T6038	9027-9032	NN	denotes	C57BL
T6039	9033-9035	NN	denotes	6J
T6040	9032-9033	HYPH	denotes	/
T6041	9050-9056	NN	denotes	Strain
T6042	9036-9038	CC	denotes	or
T6043	9039-9044	NN	denotes	C57BL
T6044	9045-9047	NN	denotes	6J
T6045	9044-9045	HYPH	denotes	/
T6046	9048-9049	SYM	denotes	×
T6047	9071-9078	NNS	denotes	embryos
T6048	9057-9064	NN	denotes	129SvEv
T6049	9065-9070	NN	denotes	mouse
T6050	9079-9081	IN	denotes	at
T6051	9082-9085	DT	denotes	the
T6052	9102-9112	NNS	denotes	facilities
T6053	9086-9096	JJ	denotes	transgenic
T6054	9097-9101	NN	denotes	core
T6055	9113-9115	IN	denotes	of
T6056	9116-9119	DT	denotes	the
T6057	9120-9130	NNP	denotes	University
T6058	9131-9133	IN	denotes	of
T6059	9134-9144	NNP	denotes	Pittsburgh
T6060	9145-9148	CC	denotes	and
T6061	9149-9152	DT	denotes	the
T6062	9153-9163	NNP	denotes	University
T6063	9164-9166	IN	denotes	of
T6064	9167-9177	NNP	denotes	Cincinnati
T6065	9177-9179	,	denotes	,
T6066	9179-9191	RB	denotes	respectively
T6067	9191-9192	.	denotes	.
T6068	9192-9389	sentence	denotes	Genomic DNA from the tail of mice was screened by Southern blot analysis following digestion with EcoRI and hybridization to an ~400 bp probe derived from the SV40 portion of the TRE-E2 transgene.
T6069	9193-9200	JJ	denotes	Genomic
T6070	9201-9204	NN	denotes	DNA
T6071	9231-9239	VBN	denotes	screened
T6072	9205-9209	IN	denotes	from
T6073	9210-9213	DT	denotes	the
T6074	9214-9218	NN	denotes	tail
T6075	9219-9221	IN	denotes	of
T6076	9222-9226	NNS	denotes	mice
T6077	9227-9230	VBD	denotes	was
T6078	9240-9242	IN	denotes	by
T6079	9243-9251	NNP	denotes	Southern
T6080	9252-9256	NN	denotes	blot
T6081	9257-9265	NN	denotes	analysis
T6082	9266-9275	VBG	denotes	following
T6083	9276-9285	NN	denotes	digestion
T6084	9286-9290	IN	denotes	with
T6085	9291-9296	NN	denotes	EcoRI
T6086	9297-9300	CC	denotes	and
T6087	9301-9314	NN	denotes	hybridization
T6088	9315-9317	IN	denotes	to
T6089	9318-9320	DT	denotes	an
T6090	9329-9334	NN	denotes	probe
T6091	9321-9322	SYM	denotes	~
T6092	9322-9325	CD	denotes	400
T6093	9326-9328	NN	denotes	bp
T6094	9335-9342	VBN	denotes	derived
T6095	9343-9347	IN	denotes	from
T6096	9348-9351	DT	denotes	the
T6097	9357-9364	NN	denotes	portion
T6098	9352-9356	NN	denotes	SV40
T6099	9365-9367	IN	denotes	of
T6100	9368-9371	DT	denotes	the
T6101	9379-9388	NN	denotes	transgene
T6102	9372-9375	NN	denotes	TRE
T6103	9376-9378	NN	denotes	E2
T6104	9375-9376	HYPH	denotes	-
T6105	9388-9389	.	denotes	.
T6426	9391-9401	NN	denotes	Production
T6427	9402-9404	IN	denotes	of
T6428	9405-9417	JJ	denotes	intermediate
T6429	9430-9435	NN	denotes	model
T6430	9418-9422	NN	denotes	MSUD
T6431	9423-9429	JJ	denotes	murine
T6432	9435-9692	sentence	denotes	The various TRE-E2 transgenic lines produced were mated independently to mice that were heterozygous for both the E2 knockout and the LAP-tTA transgene [Tg(tTALap)Bjd/J; Stock 3272; The Jackson Laboratory, Bar Harbor, ME; NMRI × FVB × C57BL/6J background].
T6433	9436-9439	DT	denotes	The
T6434	9466-9471	NNS	denotes	lines
T6435	9440-9447	JJ	denotes	various
T6436	9448-9451	NN	denotes	TRE
T6437	9452-9454	NN	denotes	E2
T6438	9451-9452	HYPH	denotes	-
T6439	9455-9465	JJ	denotes	transgenic
T6440	9486-9491	VBN	denotes	mated
T6441	9472-9480	VBN	denotes	produced
T6442	9481-9485	VBD	denotes	were
T6443	9492-9505	RB	denotes	independently
T6444	9506-9508	IN	denotes	to
T6445	9509-9513	NNS	denotes	mice
T6446	9514-9518	WDT	denotes	that
T6447	9519-9523	VBD	denotes	were
T6448	9524-9536	JJ	denotes	heterozygous
T6449	9537-9540	IN	denotes	for
T6450	9541-9545	CC	denotes	both
T6451	9553-9561	NN	denotes	knockout
T6452	9546-9549	DT	denotes	the
T6453	9550-9552	NN	denotes	E2
T6454	9562-9565	CC	denotes	and
T6455	9566-9569	DT	denotes	the
T6456	9578-9587	NN	denotes	transgene
T6457	9570-9573	NN	denotes	LAP
T6458	9574-9577	NN	denotes	tTA
T6459	9573-9574	HYPH	denotes	-
T6460	9588-9589	-LRB-	denotes	[
T6461	9680-9690	NN	denotes	background
T6462	9589-9591	NN	denotes	Tg
T6463	9606-9611	NN	denotes	Stock
T6464	9591-9592	-LRB-	denotes	(
T6465	9592-9598	NN	denotes	tTALap
T6466	9598-9599	-RRB-	denotes	)
T6467	9599-9602	NN	denotes	Bjd
T6468	9603-9604	NN	denotes	J
T6469	9602-9603	HYPH	denotes	/
T6470	9604-9605	:	denotes	;
T6471	9612-9616	CD	denotes	3272
T6472	9616-9617	:	denotes	;
T6473	9618-9621	DT	denotes	The
T6474	9630-9640	NNP	denotes	Laboratory
T6475	9622-9629	NNP	denotes	Jackson
T6476	9640-9642	,	denotes	,
T6477	9642-9645	NNP	denotes	Bar
T6478	9646-9652	NNP	denotes	Harbor
T6479	9652-9654	,	denotes	,
T6480	9654-9656	NNP	denotes	ME
T6481	9656-9657	:	denotes	;
T6482	9658-9662	NN	denotes	NMRI
T6483	9663-9664	SYM	denotes	×
T6484	9665-9668	NN	denotes	FVB
T6485	9669-9670	SYM	denotes	×
T6486	9671-9676	NN	denotes	C57BL
T6487	9677-9679	NN	denotes	6J
T6488	9676-9677	HYPH	denotes	/
T6489	9690-9691	-RRB-	denotes	]
T6490	9691-9692	.	denotes	.
T6491	9692-9993	sentence	denotes	Interbreeding of animals that were heterozygous for both transgenes and the knockout resulted in the production of mice with a variety of genotypes including some animals that were homozygous for the knockout and were positive for both transgenes (we refer to this genotype as the "rescue" genotype).
T6492	9693-9706	NN	denotes	Interbreeding
T6493	9778-9786	VBD	denotes	resulted
T6494	9707-9709	IN	denotes	of
T6495	9710-9717	NNS	denotes	animals
T6496	9718-9722	WDT	denotes	that
T6497	9723-9727	VBD	denotes	were
T6498	9728-9740	JJ	denotes	heterozygous
T6499	9741-9744	IN	denotes	for
T6500	9745-9749	DT	denotes	both
T6501	9750-9760	NNS	denotes	transgenes
T6502	9761-9764	CC	denotes	and
T6503	9765-9768	DT	denotes	the
T6504	9769-9777	NN	denotes	knockout
T6505	9787-9789	IN	denotes	in
T6506	9790-9793	DT	denotes	the
T6507	9794-9804	NN	denotes	production
T6508	9805-9807	IN	denotes	of
T6509	9808-9812	NNS	denotes	mice
T6510	9813-9817	IN	denotes	with
T6511	9818-9819	DT	denotes	a
T6512	9820-9827	NN	denotes	variety
T6513	9828-9830	IN	denotes	of
T6514	9831-9840	NNS	denotes	genotypes
T6515	9841-9850	VBG	denotes	including
T6516	9851-9855	DT	denotes	some
T6517	9856-9863	NNS	denotes	animals
T6518	9864-9868	WDT	denotes	that
T6519	9869-9873	VBD	denotes	were
T6520	9874-9884	JJ	denotes	homozygous
T6521	9885-9888	IN	denotes	for
T6522	9889-9892	DT	denotes	the
T6523	9893-9901	NN	denotes	knockout
T6524	9902-9905	CC	denotes	and
T6525	9906-9910	VBD	denotes	were
T6526	9911-9919	JJ	denotes	positive
T6527	9920-9923	IN	denotes	for
T6528	9924-9928	DT	denotes	both
T6529	9929-9939	NNS	denotes	transgenes
T6530	9940-9941	-LRB-	denotes	(
T6531	9944-9949	VBP	denotes	refer
T6532	9941-9943	PRP	denotes	we
T6533	9950-9952	IN	denotes	to
T6534	9953-9957	DT	denotes	this
T6535	9958-9966	NN	denotes	genotype
T6536	9967-9969	IN	denotes	as
T6537	9970-9973	DT	denotes	the
T6538	9983-9991	NN	denotes	genotype
T6539	9974-9975	``	denotes	"
T6540	9975-9981	NN	denotes	rescue
T6541	9981-9982	''	denotes	"
T6542	9991-9992	-RRB-	denotes	)
T6543	9992-9993	.	denotes	.
T6544	9993-10191	sentence	denotes	If our strategy for rescuing the neonatal lethal phenotype of the knockout were successful, then those homozygous knockout animals that had both transgenes would survive beyond the neonatal period.
T6545	9994-9996	IN	denotes	If
T6546	10069-10073	VBD	denotes	were
T6547	9997-10000	PRP$	denotes	our
T6548	10001-10009	NN	denotes	strategy
T6549	10010-10013	IN	denotes	for
T6550	10014-10022	VBG	denotes	rescuing
T6551	10023-10026	DT	denotes	the
T6552	10043-10052	NN	denotes	phenotype
T6553	10027-10035	JJ	denotes	neonatal
T6554	10036-10042	JJ	denotes	lethal
T6555	10053-10055	IN	denotes	of
T6556	10056-10059	DT	denotes	the
T6557	10060-10068	NN	denotes	knockout
T6558	10156-10163	VB	denotes	survive
T6559	10074-10084	JJ	denotes	successful
T6560	10084-10086	,	denotes	,
T6561	10086-10090	RB	denotes	then
T6562	10091-10096	DT	denotes	those
T6563	10117-10124	NNS	denotes	animals
T6564	10097-10107	JJ	denotes	homozygous
T6565	10108-10116	NN	denotes	knockout
T6566	10125-10129	WDT	denotes	that
T6567	10130-10133	VBD	denotes	had
T6568	10134-10138	DT	denotes	both
T6569	10139-10149	NNS	denotes	transgenes
T6570	10150-10155	MD	denotes	would
T6571	10164-10170	IN	denotes	beyond
T6572	10171-10174	DT	denotes	the
T6573	10184-10190	NN	denotes	period
T6574	10175-10183	JJ	denotes	neonatal
T6575	10190-10191	.	denotes	.
T6670	10193-10203	NN	denotes	Genotyping
T6671	10203-10254	sentence	denotes	All mice were genotyped by Southern blot analysis.
T6672	10204-10207	DT	denotes	All
T6673	10208-10212	NNS	denotes	mice
T6674	10218-10227	VBN	denotes	genotyped
T6675	10213-10217	VBD	denotes	were
T6676	10228-10230	IN	denotes	by
T6677	10231-10239	NNP	denotes	Southern
T6678	10240-10244	NN	denotes	blot
T6679	10245-10253	NN	denotes	analysis
T6680	10253-10254	.	denotes	.
T6681	10254-10452	sentence	denotes	Genomic DNAs prepared from tail snips were digested with an appropriate restriction enzyme, size fractionated by agarose gel electrophoresis, blotted to nylon, and probed using standard procedures.
T6682	10255-10262	JJ	denotes	Genomic
T6683	10263-10267	NNS	denotes	DNAs
T6684	10298-10306	VBN	denotes	digested
T6685	10268-10276	VBN	denotes	prepared
T6686	10277-10281	IN	denotes	from
T6687	10282-10286	NN	denotes	tail
T6688	10287-10292	NNS	denotes	snips
T6689	10293-10297	VBD	denotes	were
T6690	10307-10311	IN	denotes	with
T6691	10312-10314	DT	denotes	an
T6692	10339-10345	NN	denotes	enzyme
T6693	10315-10326	JJ	denotes	appropriate
T6694	10327-10338	NN	denotes	restriction
T6695	10345-10347	,	denotes	,
T6696	10347-10351	NN	denotes	size
T6697	10352-10364	VBN	denotes	fractionated
T6698	10365-10367	IN	denotes	by
T6699	10368-10375	NN	denotes	agarose
T6700	10376-10379	NN	denotes	gel
T6701	10380-10395	NN	denotes	electrophoresis
T6702	10395-10397	,	denotes	,
T6703	10397-10404	VBN	denotes	blotted
T6704	10405-10407	IN	denotes	to
T6705	10408-10413	NN	denotes	nylon
T6706	10413-10415	,	denotes	,
T6707	10415-10418	CC	denotes	and
T6708	10419-10425	VBN	denotes	probed
T6709	10426-10431	VBG	denotes	using
T6710	10432-10440	JJ	denotes	standard
T6711	10441-10451	NNS	denotes	procedures
T6712	10451-10452	.	denotes	.
T7183	10454-10474	NN	denotes	Immunohistochemistry
T7184	10474-10581	sentence	denotes	Primary mouse embryonic fibroblasts were prepared from embryonic day ~16.5–18.5 fetuses as described [29].
T7185	10475-10482	JJ	denotes	Primary
T7186	10499-10510	NNS	denotes	fibroblasts
T7187	10483-10488	NN	denotes	mouse
T7188	10489-10498	JJ	denotes	embryonic
T7189	10516-10524	VBN	denotes	prepared
T7190	10511-10515	VBD	denotes	were
T7191	10525-10529	IN	denotes	from
T7192	10530-10539	JJ	denotes	embryonic
T7193	10555-10562	NNS	denotes	fetuses
T7194	10540-10543	NN	denotes	day
T7195	10545-10549	CD	denotes	16.5
T7196	10544-10545	SYM	denotes	~
T7197	10549-10550	SYM	denotes	–
T7198	10550-10554	CD	denotes	18.5
T7199	10563-10565	IN	denotes	as
T7200	10566-10575	VBN	denotes	described
T7201	10576-10577	-LRB-	denotes	[
T7202	10577-10579	CD	denotes	29
T7203	10579-10580	-RRB-	denotes	]
T7204	10580-10581	.	denotes	.
T7205	10581-10837	sentence	denotes	Fibroblasts were passed onto glass, fixed in 2% paraformaldehyde in PBS for 10 minutes, permeabilized in 2% paraformaldehyde containing 0.1% Triton X100 for 10 minutes and washed three times in PBS containing 0.5% BSA and 0.15% glycine, pH 7.4 (Buffer A).
T7206	10582-10593	NNS	denotes	Fibroblasts
T7207	10599-10605	VBN	denotes	passed
T7208	10594-10598	VBD	denotes	were
T7209	10606-10610	IN	denotes	onto
T7210	10611-10616	NN	denotes	glass
T7211	10616-10618	,	denotes	,
T7212	10618-10623	VBN	denotes	fixed
T7213	10624-10626	IN	denotes	in
T7214	10627-10628	CD	denotes	2
T7215	10628-10629	NN	denotes	%
T7216	10630-10646	NN	denotes	paraformaldehyde
T7217	10647-10649	IN	denotes	in
T7218	10650-10653	NN	denotes	PBS
T7219	10654-10657	IN	denotes	for
T7220	10658-10660	CD	denotes	10
T7221	10661-10668	NNS	denotes	minutes
T7222	10668-10670	,	denotes	,
T7223	10670-10683	VBN	denotes	permeabilized
T7224	10684-10686	IN	denotes	in
T7225	10687-10688	CD	denotes	2
T7226	10688-10689	NN	denotes	%
T7227	10690-10706	NN	denotes	paraformaldehyde
T7228	10707-10717	VBG	denotes	containing
T7229	10718-10721	CD	denotes	0.1
T7230	10721-10722	NN	denotes	%
T7231	10730-10734	NN	denotes	X100
T7232	10723-10729	NN	denotes	Triton
T7233	10735-10738	IN	denotes	for
T7234	10739-10741	CD	denotes	10
T7235	10742-10749	NNS	denotes	minutes
T7236	10750-10753	CC	denotes	and
T7237	10754-10760	VBD	denotes	washed
T7238	10761-10766	CD	denotes	three
T7239	10767-10772	NNS	denotes	times
T7240	10773-10775	IN	denotes	in
T7241	10776-10779	NN	denotes	PBS
T7242	10780-10790	VBG	denotes	containing
T7243	10791-10794	CD	denotes	0.5
T7244	10794-10795	NN	denotes	%
T7245	10796-10799	NN	denotes	BSA
T7246	10800-10803	CC	denotes	and
T7247	10804-10808	CD	denotes	0.15
T7248	10808-10809	NN	denotes	%
T7249	10810-10817	NN	denotes	glycine
T7250	10817-10819	,	denotes	,
T7251	10819-10821	NN	denotes	pH
T7252	10822-10825	CD	denotes	7.4
T7253	10826-10827	-LRB-	denotes	(
T7254	10834-10835	NN	denotes	A
T7255	10827-10833	NN	denotes	Buffer
T7256	10835-10836	-RRB-	denotes	)
T7257	10836-10837	.	denotes	.
T7258	10837-11144	sentence	denotes	Following a 30 min incubation with purified goat IgG (50 (μg/ml) at 25°C and three additional washes with Buffer A, cells were incubated for 60 min with E2-specific antiserum [30] at 1 μg/ml followed by three washes in Buffer A and 60 minute incubation in fluorescently labeled second antibody (1–2 μg/ml).
T7259	10838-10847	VBG	denotes	Following
T7260	10965-10974	VBN	denotes	incubated
T7261	10848-10849	DT	denotes	a
T7262	10857-10867	NN	denotes	incubation
T7263	10850-10852	CD	denotes	30
T7264	10853-10856	NN	denotes	min
T7265	10868-10872	IN	denotes	with
T7266	10873-10881	VBN	denotes	purified
T7267	10887-10890	NN	denotes	IgG
T7268	10882-10886	NN	denotes	goat
T7269	10891-10892	-LRB-	denotes	(
T7270	10896-10898	NN	denotes	μg
T7271	10892-10894	CD	denotes	50
T7272	10895-10896	-LRB-	denotes	(
T7273	10898-10899	SYM	denotes	/
T7274	10899-10901	NN	denotes	ml
T7275	10901-10902	-RRB-	denotes	)
T7276	10903-10905	IN	denotes	at
T7277	10906-10908	CD	denotes	25
T7278	10908-10910	NN	denotes	°C
T7279	10911-10914	CC	denotes	and
T7280	10915-10920	CD	denotes	three
T7281	10932-10938	NNS	denotes	washes
T7282	10921-10931	JJ	denotes	additional
T7283	10939-10943	IN	denotes	with
T7284	10944-10950	NN	denotes	Buffer
T7285	10951-10952	NN	denotes	A
T7286	10952-10954	,	denotes	,
T7287	10954-10959	NNS	denotes	cells
T7288	10960-10964	VBD	denotes	were
T7289	10975-10978	IN	denotes	for
T7290	10979-10981	CD	denotes	60
T7291	10982-10985	NN	denotes	min
T7292	10986-10990	IN	denotes	with
T7293	10991-10993	NN	denotes	E2
T7294	10994-11002	JJ	denotes	specific
T7295	10993-10994	HYPH	denotes	-
T7296	11003-11012	NN	denotes	antiserum
T7297	11013-11014	-LRB-	denotes	[
T7298	11014-11016	CD	denotes	30
T7299	11016-11017	-RRB-	denotes	]
T7300	11018-11020	IN	denotes	at
T7301	11021-11022	CD	denotes	1
T7302	11023-11025	NN	denotes	μg
T7303	11025-11026	SYM	denotes	/
T7304	11026-11028	NN	denotes	ml
T7305	11029-11037	VBN	denotes	followed
T7306	11038-11040	IN	denotes	by
T7307	11041-11046	CD	denotes	three
T7308	11047-11053	NNS	denotes	washes
T7309	11054-11056	IN	denotes	in
T7310	11057-11063	NN	denotes	Buffer
T7311	11064-11065	NN	denotes	A
T7312	11066-11069	CC	denotes	and
T7313	11070-11072	CD	denotes	60
T7314	11073-11079	NN	denotes	minute
T7315	11080-11090	NN	denotes	incubation
T7316	11091-11093	IN	denotes	in
T7317	11094-11107	RB	denotes	fluorescently
T7318	11108-11115	VBN	denotes	labeled
T7319	11123-11131	NN	denotes	antibody
T7320	11116-11122	JJ	denotes	second
T7321	11132-11133	-LRB-	denotes	(
T7322	11137-11139	NN	denotes	μg
T7323	11133-11134	CD	denotes	1
T7324	11135-11136	CD	denotes	2
T7325	11134-11135	SYM	denotes	–
T7326	11139-11140	SYM	denotes	/
T7327	11140-11142	NN	denotes	ml
T7328	11142-11143	-RRB-	denotes	)
T7329	11143-11144	.	denotes	.
T7330	11144-11257	sentence	denotes	The cells were then washed six times (5 min/wash) in Buffer A and then mounted in gelvatol (Monsanto, St Louis).
T7331	11145-11148	DT	denotes	The
T7332	11149-11154	NNS	denotes	cells
T7333	11165-11171	VBN	denotes	washed
T7334	11155-11159	VBD	denotes	were
T7335	11160-11164	RB	denotes	then
T7336	11172-11175	CD	denotes	six
T7337	11176-11181	NNS	denotes	times
T7338	11182-11183	-LRB-	denotes	(
T7339	11185-11188	NN	denotes	min
T7340	11183-11184	CD	denotes	5
T7341	11188-11189	SYM	denotes	/
T7342	11189-11193	NN	denotes	wash
T7343	11193-11194	-RRB-	denotes	)
T7344	11195-11197	IN	denotes	in
T7345	11198-11204	NN	denotes	Buffer
T7346	11205-11206	NN	denotes	A
T7347	11207-11210	CC	denotes	and
T7348	11211-11215	RB	denotes	then
T7349	11216-11223	VBN	denotes	mounted
T7350	11224-11226	IN	denotes	in
T7351	11227-11235	NN	denotes	gelvatol
T7352	11236-11237	-LRB-	denotes	(
T7353	11237-11245	NNP	denotes	Monsanto
T7354	11245-11247	,	denotes	,
T7355	11247-11249	NNP	denotes	St
T7356	11250-11255	NNP	denotes	Louis
T7357	11255-11256	-RRB-	denotes	)
T7358	11256-11257	.	denotes	.
T7359	11257-11462	sentence	denotes	When livers from newborn pups were examined, fixation was by immersion in 2% paraformaldehyde followed by cryoprotection and shock freezing in liquid nitrogen cooled isopentane and sectioning (5 microns).
T7360	11258-11262	WRB	denotes	When
T7361	11293-11301	VBN	denotes	examined
T7362	11263-11269	NNS	denotes	livers
T7363	11270-11274	IN	denotes	from
T7364	11275-11282	JJ	denotes	newborn
T7365	11283-11287	NNS	denotes	pups
T7366	11288-11292	VBD	denotes	were
T7367	11312-11315	VBD	denotes	was
T7368	11301-11303	,	denotes	,
T7369	11303-11311	NN	denotes	fixation
T7370	11316-11318	IN	denotes	by
T7371	11319-11328	NN	denotes	immersion
T7372	11329-11331	IN	denotes	in
T7373	11332-11333	CD	denotes	2
T7374	11333-11334	NN	denotes	%
T7375	11335-11351	NN	denotes	paraformaldehyde
T7376	11352-11360	VBN	denotes	followed
T7377	11361-11363	IN	denotes	by
T7378	11364-11378	NN	denotes	cryoprotection
T7379	11379-11382	CC	denotes	and
T7380	11383-11388	NN	denotes	shock
T7381	11389-11397	NN	denotes	freezing
T7382	11398-11400	IN	denotes	in
T7383	11401-11407	JJ	denotes	liquid
T7384	11408-11416	NN	denotes	nitrogen
T7385	11417-11423	VBN	denotes	cooled
T7386	11424-11434	NN	denotes	isopentane
T7387	11435-11438	CC	denotes	and
T7388	11439-11449	NN	denotes	sectioning
T7389	11450-11451	-LRB-	denotes	(
T7390	11453-11460	NNS	denotes	microns
T7391	11451-11452	CD	denotes	5
T7392	11460-11461	-RRB-	denotes	)
T7393	11461-11462	.	denotes	.
T7394	11462-11560	sentence	denotes	Otherwise processing was as for the cells above (without the fixation and permabilization steps).
T7395	11463-11472	RB	denotes	Otherwise
T7396	11484-11487	VBD	denotes	was
T7397	11473-11483	NN	denotes	processing
T7398	11488-11490	IN	denotes	as
T7399	11491-11494	IN	denotes	for
T7400	11495-11498	DT	denotes	the
T7401	11499-11504	NNS	denotes	cells
T7402	11505-11510	RB	denotes	above
T7403	11511-11512	-LRB-	denotes	(
T7404	11512-11519	IN	denotes	without
T7405	11520-11523	DT	denotes	the
T7406	11553-11558	NNS	denotes	steps
T7407	11524-11532	NN	denotes	fixation
T7408	11533-11536	CC	denotes	and
T7409	11537-11552	NN	denotes	permabilization
T7410	11558-11559	-RRB-	denotes	)
T7411	11559-11560	.	denotes	.
T7545	11562-11567	NN	denotes	Amino
T7546	11568-11572	NN	denotes	acid
T7547	11573-11581	NN	denotes	analysis
T7548	11581-11749	sentence	denotes	Blood was collected from the retroorbital sinus or tail vein of mice and spotted on a filter paper routinely used for blood amino acid analysis for prenatal screening.
T7549	11582-11587	NN	denotes	Blood
T7550	11592-11601	VBN	denotes	collected
T7551	11588-11591	VBD	denotes	was
T7552	11602-11606	IN	denotes	from
T7553	11607-11610	DT	denotes	the
T7554	11638-11642	NN	denotes	vein
T7555	11611-11623	JJ	denotes	retroorbital
T7556	11624-11629	NN	denotes	sinus
T7557	11630-11632	CC	denotes	or
T7558	11633-11637	NN	denotes	tail
T7559	11643-11645	IN	denotes	of
T7560	11646-11650	NNS	denotes	mice
T7561	11651-11654	CC	denotes	and
T7562	11655-11662	VBN	denotes	spotted
T7563	11663-11665	IN	denotes	on
T7564	11666-11667	DT	denotes	a
T7565	11675-11680	NN	denotes	paper
T7566	11668-11674	NN	denotes	filter
T7567	11681-11690	RB	denotes	routinely
T7568	11691-11695	VBN	denotes	used
T7569	11696-11699	IN	denotes	for
T7570	11700-11705	NN	denotes	blood
T7571	11717-11725	NN	denotes	analysis
T7572	11706-11711	NN	denotes	amino
T7573	11712-11716	NN	denotes	acid
T7574	11726-11729	IN	denotes	for
T7575	11730-11738	JJ	denotes	prenatal
T7576	11739-11748	NN	denotes	screening
T7577	11748-11749	.	denotes	.
T7578	11749-11887	sentence	denotes	Concentrations of BCAA and other amino acids in blood were determined by tandem mass spectrometry (Pediatrix Screening, Bridgeville, PA).
T7579	11750-11764	NNS	denotes	Concentrations
T7580	11809-11819	VBN	denotes	determined
T7581	11765-11767	IN	denotes	of
T7582	11768-11772	NN	denotes	BCAA
T7583	11773-11776	CC	denotes	and
T7584	11777-11782	JJ	denotes	other
T7585	11789-11794	NNS	denotes	acids
T7586	11783-11788	NN	denotes	amino
T7587	11795-11797	IN	denotes	in
T7588	11798-11803	NN	denotes	blood
T7589	11804-11808	VBD	denotes	were
T7590	11820-11822	IN	denotes	by
T7591	11823-11829	JJ	denotes	tandem
T7592	11835-11847	NN	denotes	spectrometry
T7593	11830-11834	NN	denotes	mass
T7594	11848-11849	-LRB-	denotes	(
T7595	11859-11868	NNP	denotes	Screening
T7596	11849-11858	NNP	denotes	Pediatrix
T7597	11868-11870	,	denotes	,
T7598	11870-11881	NNP	denotes	Bridgeville
T7599	11881-11883	,	denotes	,
T7600	11883-11885	NNP	denotes	PA
T7601	11885-11886	-RRB-	denotes	)
T7602	11886-11887	.	denotes	.
T8105	11889-11894	NN	denotes	Assay
T8106	11895-11897	IN	denotes	of
T8107	11898-11903	NN	denotes	BCKDH
T8108	11904-11912	NN	denotes	activity
T8109	11912-11981	sentence	denotes	Livers were removed, frozen in liquid nitrogen, and stored at -80°C.
T8110	11913-11919	NNS	denotes	Livers
T8111	11925-11932	VBN	denotes	removed
T8112	11920-11924	VBD	denotes	were
T8113	11932-11934	,	denotes	,
T8114	11934-11940	VBN	denotes	frozen
T8115	11941-11943	IN	denotes	in
T8116	11944-11950	JJ	denotes	liquid
T8117	11951-11959	NN	denotes	nitrogen
T8118	11959-11961	,	denotes	,
T8119	11961-11964	CC	denotes	and
T8120	11965-11971	VBN	denotes	stored
T8121	11972-11974	IN	denotes	at
T8122	11975-11976	HYPH	denotes	-
T8123	11976-11978	CD	denotes	80
T8124	11978-11980	NN	denotes	°C
T8125	11980-11981	.	denotes	.
T8126	11981-12100	sentence	denotes	At the time of enzyme assay, livers were thawed, and homogenized (1:9, w/v) in 0.25 M sucrose, 10 mM Tris-HC1, pH 7.4.
T8127	11982-11984	IN	denotes	At
T8128	12023-12029	VBN	denotes	thawed
T8129	11985-11988	DT	denotes	the
T8130	11989-11993	NN	denotes	time
T8131	11994-11996	IN	denotes	of
T8132	11997-12003	NN	denotes	enzyme
T8133	12004-12009	NN	denotes	assay
T8134	12009-12011	,	denotes	,
T8135	12011-12017	NNS	denotes	livers
T8136	12018-12022	VBD	denotes	were
T8137	12029-12031	,	denotes	,
T8138	12031-12034	CC	denotes	and
T8139	12035-12046	VBN	denotes	homogenized
T8140	12047-12048	-LRB-	denotes	(
T8141	12055-12056	NN	denotes	v
T8142	12048-12049	CD	denotes	1
T8143	12050-12051	CD	denotes	9
T8144	12049-12050	SYM	denotes	:
T8145	12051-12053	,	denotes	,
T8146	12053-12054	NN	denotes	w
T8147	12054-12055	HYPH	denotes	/
T8148	12056-12057	-RRB-	denotes	)
T8149	12058-12060	IN	denotes	in
T8150	12061-12065	CD	denotes	0.25
T8151	12066-12067	NN	denotes	M
T8152	12068-12075	NN	denotes	sucrose
T8153	12075-12077	,	denotes	,
T8154	12077-12079	CD	denotes	10
T8155	12080-12082	NN	denotes	mM
T8156	12088-12091	NN	denotes	HC1
T8157	12083-12087	NN	denotes	Tris
T8158	12087-12088	HYPH	denotes	-
T8159	12091-12093	,	denotes	,
T8160	12093-12095	NN	denotes	pH
T8161	12096-12099	CD	denotes	7.4
T8162	12099-12100	.	denotes	.
T8163	12100-12236	sentence	denotes	Liver homogenates were centrifuged at 600 × g for 10 min at 4°C and the supernatant fraction was saved to determine the BCKDH activity.
T8164	12101-12106	NN	denotes	Liver
T8165	12107-12118	NNS	denotes	homogenates
T8166	12124-12135	VBN	denotes	centrifuged
T8167	12119-12123	VBD	denotes	were
T8168	12136-12138	IN	denotes	at
T8169	12139-12142	CD	denotes	600
T8170	12145-12146	NN	denotes	g
T8171	12143-12144	SYM	denotes	×
T8172	12147-12150	IN	denotes	for
T8173	12151-12153	CD	denotes	10
T8174	12154-12157	NN	denotes	min
T8175	12158-12160	IN	denotes	at
T8176	12161-12162	CD	denotes	4
T8177	12162-12164	NN	denotes	°C
T8178	12165-12168	CC	denotes	and
T8179	12169-12172	DT	denotes	the
T8180	12185-12193	NN	denotes	fraction
T8181	12173-12184	NN	denotes	supernatant
T8182	12198-12203	VBN	denotes	saved
T8183	12194-12197	VBD	denotes	was
T8184	12204-12206	TO	denotes	to
T8185	12207-12216	VB	denotes	determine
T8186	12217-12220	DT	denotes	the
T8187	12227-12235	NN	denotes	activity
T8188	12221-12226	NN	denotes	BCKDH
T8189	12235-12236	.	denotes	.
T8190	12236-12360	sentence	denotes	The use of tissue homogenates was necessitated by the limited availability of liver tissue, particularly from newborn pups.
T8191	12237-12240	DT	denotes	The
T8192	12241-12244	NN	denotes	use
T8193	12271-12283	VBN	denotes	necessitated
T8194	12245-12247	IN	denotes	of
T8195	12248-12254	NN	denotes	tissue
T8196	12255-12266	NNS	denotes	homogenates
T8197	12267-12270	VBD	denotes	was
T8198	12284-12286	IN	denotes	by
T8199	12287-12290	DT	denotes	the
T8200	12299-12311	NN	denotes	availability
T8201	12291-12298	JJ	denotes	limited
T8202	12312-12314	IN	denotes	of
T8203	12315-12320	NN	denotes	liver
T8204	12321-12327	NN	denotes	tissue
T8205	12327-12329	,	denotes	,
T8206	12329-12341	RB	denotes	particularly
T8207	12342-12346	IN	denotes	from
T8208	12347-12354	JJ	denotes	newborn
T8209	12355-12359	NNS	denotes	pups
T8210	12359-12360	.	denotes	.
T8211	12360-12486	sentence	denotes	BCKDH activity was determined by measuring the release of 14CO2 from α-keto [1-14C] isocaproate as described previously [31].
T8212	12361-12366	NN	denotes	BCKDH
T8213	12367-12375	NN	denotes	activity
T8214	12380-12390	VBN	denotes	determined
T8215	12376-12379	VBD	denotes	was
T8216	12391-12393	IN	denotes	by
T8217	12394-12403	VBG	denotes	measuring
T8218	12404-12407	DT	denotes	the
T8219	12408-12415	NN	denotes	release
T8220	12416-12418	IN	denotes	of
T8221	12419-12424	NN	denotes	14CO2
T8222	12425-12429	IN	denotes	from
T8223	12430-12431	NN	denotes	α
T8224	12432-12436	NN	denotes	keto
T8225	12431-12432	HYPH	denotes	-
T8226	12445-12456	NN	denotes	isocaproate
T8227	12437-12438	-LRB-	denotes	[
T8228	12438-12439	CD	denotes	1
T8229	12439-12440	SYM	denotes	-
T8230	12440-12443	NN	denotes	14C
T8231	12443-12444	-RRB-	denotes	]
T8232	12457-12459	IN	denotes	as
T8233	12460-12469	VBN	denotes	described
T8234	12470-12480	RB	denotes	previously
T8235	12481-12482	-LRB-	denotes	[
T8236	12482-12484	CD	denotes	31
T8237	12484-12485	-RRB-	denotes	]
T8238	12485-12486	.	denotes	.
T8239	12486-12811	sentence	denotes	The complete reaction mixture contained (final volume 1 ml) 30 mM potassium phosphate buffer, pH 7.4, 0.20 mM α-ketoisocaproate, 0.40 mM CoASH, 0.40 mM thiamin pyrophosphate, 2 mM NAD+, 2 mM dithiothreitol, 5 mM Mg2+, approximately 250,000 DPM of α-keto [1-14C] isocaproate, and 0.10 ml of liver homogenate (2–3 mg protein).
T8240	12487-12490	DT	denotes	The
T8241	12509-12516	NN	denotes	mixture
T8242	12491-12499	JJ	denotes	complete
T8243	12500-12508	NN	denotes	reaction
T8244	12517-12526	VBD	denotes	contained
T8245	12527-12528	-LRB-	denotes	(
T8246	12534-12540	NN	denotes	volume
T8247	12528-12533	JJ	denotes	final
T8248	12541-12542	CD	denotes	1
T8249	12543-12545	NN	denotes	ml
T8250	12545-12546	-RRB-	denotes	)
T8251	12547-12549	CD	denotes	30
T8252	12550-12552	NN	denotes	mM
T8253	12573-12579	NN	denotes	buffer
T8254	12553-12562	NN	denotes	potassium
T8255	12563-12572	NN	denotes	phosphate
T8256	12579-12581	,	denotes	,
T8257	12581-12583	NN	denotes	pH
T8258	12584-12587	CD	denotes	7.4
T8259	12587-12589	,	denotes	,
T8260	12589-12593	CD	denotes	0.20
T8261	12594-12596	NN	denotes	mM
T8262	12599-12614	NN	denotes	ketoisocaproate
T8263	12597-12598	NN	denotes	α
T8264	12598-12599	HYPH	denotes	-
T8265	12614-12616	,	denotes	,
T8266	12616-12620	CD	denotes	0.40
T8267	12621-12623	NN	denotes	mM
T8268	12624-12629	NN	denotes	CoASH
T8269	12629-12631	,	denotes	,
T8270	12631-12635	CD	denotes	0.40
T8271	12636-12638	NN	denotes	mM
T8272	12647-12660	NN	denotes	pyrophosphate
T8273	12639-12646	NN	denotes	thiamin
T8274	12660-12662	,	denotes	,
T8275	12662-12663	CD	denotes	2
T8276	12664-12666	NN	denotes	mM
T8277	12667-12670	NN	denotes	NAD
T8278	12670-12671	SYM	denotes	+
T8279	12671-12673	,	denotes	,
T8280	12673-12674	CD	denotes	2
T8281	12675-12677	NN	denotes	mM
T8282	12678-12692	NN	denotes	dithiothreitol
T8283	12692-12694	,	denotes	,
T8284	12694-12695	CD	denotes	5
T8285	12696-12698	NN	denotes	mM
T8286	12699-12702	NN	denotes	Mg2
T8287	12702-12703	SYM	denotes	+
T8288	12703-12705	,	denotes	,
T8289	12705-12718	RB	denotes	approximately
T8290	12719-12726	CD	denotes	250,000
T8291	12727-12730	NN	denotes	DPM
T8292	12731-12733	IN	denotes	of
T8293	12734-12735	NN	denotes	α
T8294	12736-12740	NN	denotes	keto
T8295	12735-12736	HYPH	denotes	-
T8296	12749-12760	NN	denotes	isocaproate
T8297	12741-12742	-LRB-	denotes	[
T8298	12742-12743	CD	denotes	1
T8299	12743-12744	SYM	denotes	-
T8300	12744-12747	NN	denotes	14C
T8301	12747-12748	-RRB-	denotes	]
T8302	12760-12762	,	denotes	,
T8303	12762-12765	CC	denotes	and
T8304	12766-12770	CD	denotes	0.10
T8305	12771-12773	NN	denotes	ml
T8306	12774-12776	IN	denotes	of
T8307	12777-12782	NN	denotes	liver
T8308	12783-12793	NN	denotes	homogenate
T8309	12794-12795	-LRB-	denotes	(
T8310	12802-12809	NN	denotes	protein
T8311	12795-12796	CD	denotes	2
T8312	12797-12798	CD	denotes	3
T8313	12796-12797	SYM	denotes	–
T8314	12799-12801	NN	denotes	mg
T8315	12809-12810	-RRB-	denotes	)
T8316	12810-12811	.	denotes	.
T8317	12811-12969	sentence	denotes	Assays were carried out for 15 min at 37°C, 14CO2 was trapped in hydroxide of Hyamine, and radioactivity was determined by liquid scintillation spectrometry.
T8318	12812-12818	NNS	denotes	Assays
T8319	12824-12831	VBN	denotes	carried
T8320	12819-12823	VBD	denotes	were
T8321	12832-12835	RP	denotes	out
T8322	12836-12839	IN	denotes	for
T8323	12840-12842	CD	denotes	15
T8324	12843-12846	NN	denotes	min
T8325	12847-12849	IN	denotes	at
T8326	12850-12852	CD	denotes	37
T8327	12852-12854	NN	denotes	°C
T8328	12854-12856	,	denotes	,
T8329	12856-12861	NN	denotes	14CO2
T8330	12866-12873	VBN	denotes	trapped
T8331	12862-12865	VBD	denotes	was
T8332	12874-12876	IN	denotes	in
T8333	12877-12886	NN	denotes	hydroxide
T8334	12887-12889	IN	denotes	of
T8335	12890-12897	NN	denotes	Hyamine
T8336	12897-12899	,	denotes	,
T8337	12899-12902	CC	denotes	and
T8338	12903-12916	NN	denotes	radioactivity
T8339	12921-12931	VBN	denotes	determined
T8340	12917-12920	VBD	denotes	was
T8341	12932-12934	IN	denotes	by
T8342	12935-12941	JJ	denotes	liquid
T8343	12942-12955	NN	denotes	scintillation
T8344	12956-12968	NN	denotes	spectrometry
T8345	12968-12969	.	denotes	.
T8817	12971-12978	NNP	denotes	Western
T8818	12979-12983	NN	denotes	blot
T8819	12984-12992	NN	denotes	analysis
T8820	12992-13135	sentence	denotes	Protein extracts were isolated from homogenized liver (freshly harvested and flash frozen) of wildtype, Line 525A, and Line A transgenic mice.
T8821	12993-13000	NN	denotes	Protein
T8822	13001-13009	NNS	denotes	extracts
T8823	13015-13023	VBN	denotes	isolated
T8824	13010-13014	VBD	denotes	were
T8825	13024-13028	IN	denotes	from
T8826	13029-13040	VBN	denotes	homogenized
T8827	13041-13046	NN	denotes	liver
T8828	13047-13048	-LRB-	denotes	(
T8829	13048-13055	RB	denotes	freshly
T8830	13056-13065	VBN	denotes	harvested
T8831	13066-13069	CC	denotes	and
T8832	13070-13075	NN	denotes	flash
T8833	13076-13082	VBN	denotes	frozen
T8834	13082-13083	-RRB-	denotes	)
T8835	13084-13086	IN	denotes	of
T8836	13087-13095	NN	denotes	wildtype
T8837	13119-13129	JJ	denotes	transgenic
T8838	13095-13097	,	denotes	,
T8839	13097-13101	NN	denotes	Line
T8840	13102-13106	NN	denotes	525A
T8841	13106-13108	,	denotes	,
T8842	13108-13111	CC	denotes	and
T8843	13112-13116	NN	denotes	Line
T8844	13117-13118	NN	denotes	A
T8845	13130-13134	NNS	denotes	mice
T8846	13134-13135	.	denotes	.
T8847	13135-13322	sentence	denotes	Protein (25 μg per sample) was analyzed by electrophoresis on a 10% SDS-PAGE Ready Gel (Bio-Rad, Hercules, CA) and transferred to PVDF membrane (Sequi-Blot; Bio-Rad) via electroblotting.
T8848	13136-13143	NN	denotes	Protein
T8849	13167-13175	VBN	denotes	analyzed
T8850	13144-13145	-LRB-	denotes	(
T8851	13148-13150	NN	denotes	μg
T8852	13145-13147	CD	denotes	25
T8853	13151-13154	IN	denotes	per
T8854	13155-13161	NN	denotes	sample
T8855	13161-13162	-RRB-	denotes	)
T8856	13163-13166	VBD	denotes	was
T8857	13176-13178	IN	denotes	by
T8858	13179-13194	NN	denotes	electrophoresis
T8859	13195-13197	IN	denotes	on
T8860	13198-13199	DT	denotes	a
T8861	13219-13222	NN	denotes	Gel
T8862	13200-13202	CD	denotes	10
T8863	13202-13203	NN	denotes	%
T8864	13204-13207	NN	denotes	SDS
T8865	13208-13212	NN	denotes	PAGE
T8866	13207-13208	HYPH	denotes	-
T8867	13213-13218	JJ	denotes	Ready
T8868	13223-13224	-LRB-	denotes	(
T8869	13228-13231	NNP	denotes	Rad
T8870	13224-13227	NNP	denotes	Bio
T8871	13227-13228	HYPH	denotes	-
T8872	13231-13233	,	denotes	,
T8873	13233-13241	NNP	denotes	Hercules
T8874	13241-13243	,	denotes	,
T8875	13243-13245	NNP	denotes	CA
T8876	13245-13246	-RRB-	denotes	)
T8877	13247-13250	CC	denotes	and
T8878	13251-13262	VBN	denotes	transferred
T8879	13263-13265	IN	denotes	to
T8880	13266-13270	NN	denotes	PVDF
T8881	13271-13279	NN	denotes	membrane
T8882	13280-13281	-LRB-	denotes	(
T8883	13297-13300	NNP	denotes	Rad
T8884	13281-13286	NNP	denotes	Sequi
T8885	13287-13291	NNP	denotes	Blot
T8886	13286-13287	HYPH	denotes	-
T8887	13291-13292	:	denotes	;
T8888	13293-13296	NNP	denotes	Bio
T8889	13296-13297	HYPH	denotes	-
T8890	13300-13301	-RRB-	denotes	)
T8891	13302-13305	IN	denotes	via
T8892	13306-13321	NN	denotes	electroblotting
T8893	13321-13322	.	denotes	.
T8894	13322-13531	sentence	denotes	All blots were probed for E2 protein using polyclonal rabbit E2 antisera (1:5,000), which detects both mouse (~47 kD) and human (~54 kD) E2 subunits ([30]; gift from Dr. Susan Hutson, Wake Forest University).
T8895	13323-13326	DT	denotes	All
T8896	13327-13332	NNS	denotes	blots
T8897	13338-13344	VBN	denotes	probed
T8898	13333-13337	VBD	denotes	were
T8899	13345-13348	IN	denotes	for
T8900	13349-13351	NN	denotes	E2
T8901	13352-13359	NN	denotes	protein
T8902	13360-13365	VBG	denotes	using
T8903	13366-13376	JJ	denotes	polyclonal
T8904	13387-13395	NNS	denotes	antisera
T8905	13377-13383	NN	denotes	rabbit
T8906	13384-13386	NN	denotes	E2
T8907	13396-13397	-LRB-	denotes	(
T8908	13399-13404	CD	denotes	5,000
T8909	13397-13398	CD	denotes	1
T8910	13398-13399	SYM	denotes	:
T8911	13404-13405	-RRB-	denotes	)
T8912	13405-13407	,	denotes	,
T8913	13407-13412	WDT	denotes	which
T8914	13413-13420	VBZ	denotes	detects
T8915	13421-13425	CC	denotes	both
T8916	13463-13471	NNS	denotes	subunits
T8917	13426-13431	NN	denotes	mouse
T8918	13432-13433	-LRB-	denotes	(
T8919	13437-13439	NN	denotes	kD
T8920	13433-13434	SYM	denotes	~
T8921	13434-13436	CD	denotes	47
T8922	13439-13440	-RRB-	denotes	)
T8923	13441-13444	CC	denotes	and
T8924	13445-13450	JJ	denotes	human
T8925	13451-13452	-LRB-	denotes	(
T8926	13456-13458	NN	denotes	kD
T8927	13452-13453	SYM	denotes	~
T8928	13453-13455	CD	denotes	54
T8929	13458-13459	-RRB-	denotes	)
T8930	13460-13462	NN	denotes	E2
T8931	13472-13473	-LRB-	denotes	(
T8932	13479-13483	NN	denotes	gift
T8933	13473-13474	-LRB-	denotes	[
T8934	13474-13476	CD	denotes	30
T8935	13476-13477	-RRB-	denotes	]
T8936	13477-13478	:	denotes	;
T8937	13484-13488	IN	denotes	from
T8938	13489-13492	NNP	denotes	Dr.
T8939	13499-13505	NNP	denotes	Hutson
T8940	13493-13498	NNP	denotes	Susan
T8941	13505-13507	,	denotes	,
T8942	13507-13511	NNP	denotes	Wake
T8943	13512-13518	NNP	denotes	Forest
T8944	13519-13529	NNP	denotes	University
T8945	13529-13530	-RRB-	denotes	)
T8946	13530-13531	.	denotes	.
T8947	13531-13642	sentence	denotes	Blots were re-probed with a rabbit anti-c-myc tag antibody (1:10,000; abCam, Cambridge, MA; cat.# ab9106-100).
T8948	13532-13537	NNS	denotes	Blots
T8949	13543-13552	VBN	denotes	re-probed
T8950	13538-13542	VBD	denotes	were
T8951	13553-13557	IN	denotes	with
T8952	13558-13559	DT	denotes	a
T8953	13582-13590	NN	denotes	antibody
T8954	13560-13566	NN	denotes	rabbit
T8955	13567-13573	JJ	denotes	anti-c
T8956	13574-13577	NN	denotes	myc
T8957	13573-13574	HYPH	denotes	-
T8958	13578-13581	NN	denotes	tag
T8959	13591-13592	-LRB-	denotes	(
T8960	13630-13636	NN	denotes	ab9106
T8961	13592-13593	CD	denotes	1
T8962	13594-13600	CD	denotes	10,000
T8963	13593-13594	SYM	denotes	:
T8964	13600-13601	:	denotes	;
T8965	13602-13607	NNP	denotes	abCam
T8966	13607-13609	,	denotes	,
T8967	13609-13618	NNP	denotes	Cambridge
T8968	13618-13620	,	denotes	,
T8969	13620-13622	NNP	denotes	MA
T8970	13622-13623	:	denotes	;
T8971	13624-13628	NN	denotes	cat.
T8972	13628-13629	SYM	denotes	#
T8973	13636-13637	HYPH	denotes	-
T8974	13637-13640	CD	denotes	100
T8975	13640-13641	-RRB-	denotes	)
T8976	13641-13642	.	denotes	.
T8977	13642-13773	sentence	denotes	Blots were also re-probed with an antibody for β-actin (43 kD; 1:10,000; abCam; cat.# ab8227-50) to allow for loading comparisons.
T8978	13643-13648	NNS	denotes	Blots
T8979	13659-13668	VBN	denotes	re-probed
T8980	13649-13653	VBD	denotes	were
T8981	13654-13658	RB	denotes	also
T8982	13669-13673	IN	denotes	with
T8983	13674-13676	DT	denotes	an
T8984	13677-13685	NN	denotes	antibody
T8985	13686-13689	IN	denotes	for
T8986	13690-13691	NN	denotes	β
T8987	13692-13697	NN	denotes	actin
T8988	13691-13692	HYPH	denotes	-
T8989	13698-13699	-LRB-	denotes	(
T8990	13729-13735	NN	denotes	ab8227
T8991	13699-13701	CD	denotes	43
T8992	13702-13704	NN	denotes	kD
T8993	13704-13705	:	denotes	;
T8994	13706-13707	CD	denotes	1
T8995	13708-13714	CD	denotes	10,000
T8996	13707-13708	SYM	denotes	:
T8997	13714-13715	:	denotes	;
T8998	13716-13721	NN	denotes	abCam
T8999	13721-13722	:	denotes	;
T9000	13723-13727	NN	denotes	cat.
T9001	13727-13728	SYM	denotes	#
T9002	13735-13736	HYPH	denotes	-
T9003	13736-13738	CD	denotes	50
T9004	13738-13739	-RRB-	denotes	)
T9005	13740-13742	TO	denotes	to
T9006	13743-13748	VB	denotes	allow
T9007	13749-13752	IN	denotes	for
T9008	13753-13760	NN	denotes	loading
T9009	13761-13772	NNS	denotes	comparisons
T9010	13772-13773	.	denotes	.
T9011	13773-14027	sentence	denotes	A goat anti-rabbit secondary antibody conjugated to horseradish peroxidase (1:10,000; Novus, Littleton, CO; cat.# NB730-H) was used for detection using the Western Lightning chemiluminescence reagent (Perkin Elmer, Boston, MA) and exposed to X-ray film.
T9012	13774-13775	DT	denotes	A
T9013	13803-13811	NN	denotes	antibody
T9014	13776-13780	NN	denotes	goat
T9015	13781-13792	JJ	denotes	anti-rabbit
T9016	13793-13802	JJ	denotes	secondary
T9017	13901-13905	VBN	denotes	used
T9018	13812-13822	VBN	denotes	conjugated
T9019	13823-13825	IN	denotes	to
T9020	13826-13837	NN	denotes	horseradish
T9021	13838-13848	NN	denotes	peroxidase
T9022	13849-13850	-LRB-	denotes	(
T9023	13894-13895	NN	denotes	H
T9024	13850-13851	CD	denotes	1
T9025	13852-13858	CD	denotes	10,000
T9026	13851-13852	SYM	denotes	:
T9027	13858-13859	:	denotes	;
T9028	13860-13865	NNP	denotes	Novus
T9029	13865-13867	,	denotes	,
T9030	13867-13876	NNP	denotes	Littleton
T9031	13876-13878	,	denotes	,
T9032	13878-13880	NNP	denotes	CO
T9033	13880-13881	:	denotes	;
T9034	13882-13886	NN	denotes	cat.
T9035	13886-13887	SYM	denotes	#
T9036	13888-13893	NN	denotes	NB730
T9037	13893-13894	HYPH	denotes	-
T9038	13895-13896	-RRB-	denotes	)
T9039	13897-13900	VBD	denotes	was
T9040	13906-13909	IN	denotes	for
T9041	13910-13919	NN	denotes	detection
T9042	13920-13925	VBG	denotes	using
T9043	13926-13929	DT	denotes	the
T9044	13966-13973	NN	denotes	reagent
T9045	13930-13937	NNP	denotes	Western
T9046	13938-13947	NNP	denotes	Lightning
T9047	13948-13965	NN	denotes	chemiluminescence
T9048	13974-13975	-LRB-	denotes	(
T9049	13982-13987	NNP	denotes	Elmer
T9050	13975-13981	NNP	denotes	Perkin
T9051	13987-13989	,	denotes	,
T9052	13989-13995	NNP	denotes	Boston
T9053	13995-13997	,	denotes	,
T9054	13997-13999	NNP	denotes	MA
T9055	13999-14000	-RRB-	denotes	)
T9056	14001-14004	CC	denotes	and
T9057	14005-14012	VBN	denotes	exposed
T9058	14013-14015	IN	denotes	to
T9059	14016-14021	NN	denotes	X-ray
T9060	14022-14026	NN	denotes	film
T9061	14026-14027	.	denotes	.
T9141	14029-14040	JJ	denotes	Statistical
T9142	14041-14049	NNS	denotes	analyses
T9143	14049-14160	sentence	denotes	All BCAA and BCKDH enzyme activity data are presented as the mean +/- the standard error of the mean (S.E.M.).
T9144	14050-14053	DT	denotes	All
T9145	14085-14089	NNS	denotes	data
T9146	14054-14058	NN	denotes	BCAA
T9147	14059-14062	CC	denotes	and
T9148	14063-14068	NN	denotes	BCKDH
T9149	14069-14075	NN	denotes	enzyme
T9150	14076-14084	NN	denotes	activity
T9151	14094-14103	VBN	denotes	presented
T9152	14090-14093	VBP	denotes	are
T9153	14104-14106	IN	denotes	as
T9154	14107-14110	DT	denotes	the
T9155	14111-14115	NN	denotes	mean
T9156	14116-14117	SYM	denotes	+
T9157	14117-14118	HYPH	denotes	/
T9158	14118-14119	SYM	denotes	-
T9159	14120-14123	DT	denotes	the
T9160	14133-14138	NN	denotes	error
T9161	14124-14132	JJ	denotes	standard
T9162	14139-14141	IN	denotes	of
T9163	14142-14145	DT	denotes	the
T9164	14146-14150	NN	denotes	mean
T9165	14151-14152	-LRB-	denotes	(
T9166	14152-14158	NN	denotes	S.E.M.
T9167	14158-14159	-RRB-	denotes	)
T9168	14159-14160	.	denotes	.
T9169	14160-14229	sentence	denotes	Differences between genotypes were compared by Student's t test[32].
T9170	14161-14172	NNS	denotes	Differences
T9171	14196-14204	VBN	denotes	compared
T9172	14173-14180	IN	denotes	between
T9173	14181-14190	NNS	denotes	genotypes
T9174	14191-14195	VBD	denotes	were
T9175	14205-14207	IN	denotes	by
T9176	14208-14215	NNP	denotes	Student
T9177	14220-14224	NN	denotes	test
T9178	14215-14217	POS	denotes	's
T9179	14218-14219	NN	denotes	t
T9180	14224-14225	-LRB-	denotes	[
T9181	14225-14227	CD	denotes	32
T9182	14227-14228	-RRB-	denotes	]
T9183	14228-14229	.	denotes	.
T10447	14632-14635	CD	denotes	522
T10367	14240-14250	NN	denotes	Production
T10368	14251-14253	IN	denotes	of
T10369	14254-14256	NN	denotes	E2
T10370	14271-14275	NNS	denotes	mice
T10371	14257-14261	NN	denotes	gene
T10372	14262-14270	NN	denotes	knockout
T10373	14275-14368	sentence	denotes	To create E2 knockout mice, we used gene targeting in mouse ES cells to disrupt the E2 gene.
T10374	14276-14278	TO	denotes	To
T10375	14279-14285	VB	denotes	create
T10376	14307-14311	VBD	denotes	used
T10377	14286-14288	NN	denotes	E2
T10378	14298-14302	NNS	denotes	mice
T10379	14289-14297	NN	denotes	knockout
T10380	14302-14304	,	denotes	,
T10381	14304-14306	PRP	denotes	we
T10382	14312-14316	NN	denotes	gene
T10383	14317-14326	NN	denotes	targeting
T10384	14327-14329	IN	denotes	in
T10385	14330-14335	NN	denotes	mouse
T10386	14339-14344	NNS	denotes	cells
T10387	14336-14338	NN	denotes	ES
T10388	14345-14347	TO	denotes	to
T10389	14348-14355	VB	denotes	disrupt
T10390	14356-14359	DT	denotes	the
T10391	14363-14367	NN	denotes	gene
T10392	14360-14362	NN	denotes	E2
T10393	14367-14368	.	denotes	.
T10394	14368-14443	sentence	denotes	The overall strategy for disrupting the E2 gene is illustrated in Fig. 1A.
T10395	14369-14372	DT	denotes	The
T10396	14381-14389	NN	denotes	strategy
T10397	14373-14380	JJ	denotes	overall
T10398	14420-14431	VBN	denotes	illustrated
T10399	14390-14393	IN	denotes	for
T10400	14394-14404	VBG	denotes	disrupting
T10401	14405-14408	DT	denotes	the
T10402	14412-14416	NN	denotes	gene
T10403	14409-14411	NN	denotes	E2
T10404	14417-14419	VBZ	denotes	is
T10405	14432-14434	IN	denotes	in
T10406	14435-14439	NN	denotes	Fig.
T10407	14440-14442	NN	denotes	1A
T10408	14442-14443	.	denotes	.
T10409	14443-14628	sentence	denotes	The gene targeting construct was designed to replace a 1.67 kb EcoRV/Smal genomic DNA fragment encompassing part of Exon 4 and all of Exon 5 with the PGKneo selectable marker cassette.
T10410	14444-14447	DT	denotes	The
T10411	14463-14472	NN	denotes	construct
T10412	14448-14452	NN	denotes	gene
T10413	14453-14462	NN	denotes	targeting
T10414	14477-14485	VBN	denotes	designed
T10415	14473-14476	VBD	denotes	was
T10416	14486-14488	TO	denotes	to
T10417	14489-14496	VB	denotes	replace
T10418	14497-14498	DT	denotes	a
T10419	14530-14538	NN	denotes	fragment
T10420	14499-14503	CD	denotes	1.67
T10421	14504-14506	NN	denotes	kb
T10422	14507-14512	NN	denotes	EcoRV
T10423	14513-14517	NN	denotes	Smal
T10424	14512-14513	HYPH	denotes	/
T10425	14518-14525	JJ	denotes	genomic
T10426	14526-14529	NN	denotes	DNA
T10427	14539-14551	VBG	denotes	encompassing
T10428	14552-14556	NN	denotes	part
T10429	14557-14559	IN	denotes	of
T10430	14560-14564	NN	denotes	Exon
T10431	14565-14566	CD	denotes	4
T10432	14567-14570	CC	denotes	and
T10433	14571-14574	DT	denotes	all
T10434	14575-14577	IN	denotes	of
T10435	14578-14582	NN	denotes	Exon
T10436	14583-14584	CD	denotes	5
T10437	14585-14589	IN	denotes	with
T10438	14590-14593	DT	denotes	the
T10439	14619-14627	NN	denotes	cassette
T10440	14594-14600	NN	denotes	PGKneo
T10441	14601-14611	JJ	denotes	selectable
T10442	14612-14618	NN	denotes	marker
T10443	14627-14628	.	denotes	.
T10444	14628-14820	sentence	denotes	Of 522 ES cell clones screened for targeting by Southern blot analysis, 29 (5%) displayed the predicted restriction fragment length polymorphisms indicative of gene targeting at the E2 locus.
T10445	14629-14631	IN	denotes	Of
T10446	14709-14718	VBD	denotes	displayed
T10448	14644-14650	NNS	denotes	clones
T10449	14636-14638	NN	denotes	ES
T10450	14639-14643	NN	denotes	cell
T10451	14651-14659	VBN	denotes	screened
T10452	14660-14663	IN	denotes	for
T10453	14664-14673	NN	denotes	targeting
T10454	14674-14676	IN	denotes	by
T10455	14677-14685	NNP	denotes	Southern
T10456	14686-14690	NN	denotes	blot
T10457	14691-14699	NN	denotes	analysis
T10458	14699-14701	,	denotes	,
T10459	14701-14703	CD	denotes	29
T10460	14704-14705	-LRB-	denotes	(
T10461	14706-14707	NN	denotes	%
T10462	14705-14706	CD	denotes	5
T10463	14707-14708	-RRB-	denotes	)
T10464	14719-14722	DT	denotes	the
T10465	14761-14774	NNS	denotes	polymorphisms
T10466	14723-14732	VBN	denotes	predicted
T10467	14733-14744	NN	denotes	restriction
T10468	14754-14760	NN	denotes	length
T10469	14745-14753	NN	denotes	fragment
T10470	14775-14785	JJ	denotes	indicative
T10471	14786-14788	IN	denotes	of
T10472	14789-14793	NN	denotes	gene
T10473	14794-14803	VBG	denotes	targeting
T10474	14804-14806	IN	denotes	at
T10475	14807-14810	DT	denotes	the
T10476	14814-14819	NN	denotes	locus
T10477	14811-14813	NN	denotes	E2
T10478	14819-14820	.	denotes	.
T10479	14820-15042	sentence	denotes	As illustrated in Fig. 1A and 1B, an E2 Exon 6 specific probe, which is external to the targeting construct, hybridizes to only a ~16 kb BglI restriction fragment from the wild type allele in the parental R1 ES cell line.
T10480	14821-14823	IN	denotes	As
T10481	14824-14835	VBN	denotes	illustrated
T10482	14930-14940	VBZ	denotes	hybridizes
T10483	14836-14838	IN	denotes	in
T10484	14839-14843	NN	denotes	Fig.
T10485	14844-14846	NN	denotes	1A
T10486	14847-14850	CC	denotes	and
T10487	14851-14853	NN	denotes	1B
T10488	14853-14855	,	denotes	,
T10489	14855-14857	DT	denotes	an
T10490	14877-14882	NN	denotes	probe
T10491	14858-14860	NN	denotes	E2
T10492	14861-14865	NN	denotes	Exon
T10493	14866-14867	CD	denotes	6
T10494	14868-14876	JJ	denotes	specific
T10495	14882-14884	,	denotes	,
T10496	14884-14889	WDT	denotes	which
T10497	14890-14892	VBZ	denotes	is
T10498	14893-14901	JJ	denotes	external
T10499	14902-14904	IN	denotes	to
T10500	14905-14908	DT	denotes	the
T10501	14919-14928	NN	denotes	construct
T10502	14909-14918	NN	denotes	targeting
T10503	14928-14930	,	denotes	,
T10504	14941-14943	IN	denotes	to
T10505	14944-14948	RB	denotes	only
T10506	14975-14983	NN	denotes	fragment
T10507	14949-14950	DT	denotes	a
T10508	14951-14952	SYM	denotes	~
T10509	14952-14954	CD	denotes	16
T10510	14955-14957	NN	denotes	kb
T10511	14958-14962	NN	denotes	BglI
T10512	14963-14974	NN	denotes	restriction
T10513	14984-14988	IN	denotes	from
T10514	14989-14992	DT	denotes	the
T10515	15003-15009	NN	denotes	allele
T10516	14993-14997	JJ	denotes	wild
T10517	14998-15002	NN	denotes	type
T10518	15010-15012	IN	denotes	in
T10519	15013-15016	DT	denotes	the
T10520	15037-15041	NN	denotes	line
T10521	15017-15025	JJ	denotes	parental
T10522	15026-15028	NN	denotes	R1
T10523	15029-15031	NN	denotes	ES
T10524	15032-15036	NN	denotes	cell
T10525	15041-15042	.	denotes	.
T10526	15042-15140	sentence	denotes	In correctly targeted ES cells, this probe also hybridizes to a ~11 kb BglI restriction fragment.
T10527	15043-15045	IN	denotes	In
T10528	15091-15101	VBZ	denotes	hybridizes
T10529	15046-15055	RB	denotes	correctly
T10530	15056-15064	VBN	denotes	targeted
T10531	15068-15073	NNS	denotes	cells
T10532	15065-15067	NN	denotes	ES
T10533	15073-15075	,	denotes	,
T10534	15075-15079	DT	denotes	this
T10535	15080-15085	NN	denotes	probe
T10536	15086-15090	RB	denotes	also
T10537	15102-15104	IN	denotes	to
T10538	15105-15106	DT	denotes	a
T10539	15131-15139	NN	denotes	fragment
T10540	15107-15108	SYM	denotes	~
T10541	15108-15110	CD	denotes	11
T10542	15111-15113	NN	denotes	kb
T10543	15114-15118	NN	denotes	BglI
T10544	15119-15130	NN	denotes	restriction
T10545	15139-15140	.	denotes	.
T10546	15140-15237	sentence	denotes	Targeting was confirmed with several additional restriction enzymes and probes (data not shown).
T10547	15141-15150	NN	denotes	Targeting
T10548	15155-15164	VBN	denotes	confirmed
T10549	15151-15154	VBD	denotes	was
T10550	15165-15169	IN	denotes	with
T10551	15170-15177	JJ	denotes	several
T10552	15201-15208	NNS	denotes	enzymes
T10553	15178-15188	JJ	denotes	additional
T10554	15189-15200	NN	denotes	restriction
T10555	15209-15212	CC	denotes	and
T10556	15213-15219	NNS	denotes	probes
T10557	15220-15221	-LRB-	denotes	(
T10558	15230-15235	VBN	denotes	shown
T10559	15221-15225	NNS	denotes	data
T10560	15226-15229	RB	denotes	not
T10561	15235-15236	-RRB-	denotes	)
T10562	15236-15237	.	denotes	.
T10563	15237-15327	sentence	denotes	Correctly targeted ES cells were microinjected into blastocysts to produce chimeric mice.
T10564	15238-15247	RB	denotes	Correctly
T10565	15248-15256	VBN	denotes	targeted
T10566	15260-15265	NNS	denotes	cells
T10567	15257-15259	NN	denotes	ES
T10568	15271-15284	VBN	denotes	microinjected
T10569	15266-15270	VBD	denotes	were
T10570	15285-15289	IN	denotes	into
T10571	15290-15301	NNS	denotes	blastocysts
T10572	15302-15304	TO	denotes	to
T10573	15305-15312	VB	denotes	produce
T10574	15313-15321	JJ	denotes	chimeric
T10575	15322-15326	NNS	denotes	mice
T10576	15326-15327	.	denotes	.
T10577	15327-15365	sentence	denotes	Chimerics were bred to C57BL/6J mice.
T10578	15328-15337	NNS	denotes	Chimerics
T10579	15343-15347	VBN	denotes	bred
T10580	15338-15342	VBD	denotes	were
T10581	15348-15350	IN	denotes	to
T10582	15351-15356	NN	denotes	C57BL
T10583	15357-15359	NN	denotes	6J
T10584	15356-15357	HYPH	denotes	/
T10585	15360-15364	NNS	denotes	mice
T10586	15364-15365	.	denotes	.
T10587	15365-15531	sentence	denotes	Following germline transmission of the targeted allele, heterozygous mice were interbred to produce wild type (+/+), heterozygous (+/-) and homozygous (-/-) animals.
T10588	15366-15375	VBG	denotes	Following
T10589	15445-15454	VBN	denotes	interbred
T10590	15376-15384	NN	denotes	germline
T10591	15385-15397	NN	denotes	transmission
T10592	15398-15400	IN	denotes	of
T10593	15401-15404	DT	denotes	the
T10594	15414-15420	NN	denotes	allele
T10595	15405-15413	VBN	denotes	targeted
T10596	15420-15422	,	denotes	,
T10597	15422-15434	JJ	denotes	heterozygous
T10598	15435-15439	NNS	denotes	mice
T10599	15440-15444	VBD	denotes	were
T10600	15455-15457	TO	denotes	to
T10601	15458-15465	VB	denotes	produce
T10602	15466-15470	JJ	denotes	wild
T10603	15471-15475	NN	denotes	type
T10604	15523-15530	NNS	denotes	animals
T10605	15476-15477	-LRB-	denotes	(
T10606	15479-15480	SYM	denotes	+
T10607	15477-15478	SYM	denotes	+
T10608	15478-15479	HYPH	denotes	/
T10609	15480-15481	-RRB-	denotes	)
T10610	15481-15483	,	denotes	,
T10611	15483-15495	JJ	denotes	heterozygous
T10612	15496-15497	-LRB-	denotes	(
T10613	15499-15500	SYM	denotes	-
T10614	15497-15498	SYM	denotes	+
T10615	15498-15499	HYPH	denotes	/
T10616	15500-15501	-RRB-	denotes	)
T10617	15502-15505	CC	denotes	and
T10618	15506-15516	JJ	denotes	homozygous
T10619	15517-15518	-LRB-	denotes	(
T10620	15520-15521	SYM	denotes	-
T10621	15518-15519	SYM	denotes	-
T10622	15519-15520	HYPH	denotes	/
T10623	15521-15522	-RRB-	denotes	)
T10624	15530-15531	.	denotes	.
T10625	15531-15578	sentence	denotes	Mice were genotyped by Southern blot analysis.
T10626	15532-15536	NNS	denotes	Mice
T10627	15542-15551	VBN	denotes	genotyped
T10628	15537-15541	VBD	denotes	were
T10629	15552-15554	IN	denotes	by
T10630	15555-15563	NNP	denotes	Southern
T10631	15564-15568	NN	denotes	blot
T10632	15569-15577	NN	denotes	analysis
T10633	15577-15578	.	denotes	.
T10634	15578-15761	sentence	denotes	The Exon 6 specific probe hybridized to only a ~16 kb BglI restriction fragment in +/+ mice, a ~11 kb BglI fragment in -/- mice, and to both of these fragments in +/- mice (Fig. 1B).
T10635	15579-15582	DT	denotes	The
T10636	15599-15604	NN	denotes	probe
T10637	15583-15587	NN	denotes	Exon
T10638	15590-15598	JJ	denotes	specific
T10639	15588-15589	CD	denotes	6
T10640	15605-15615	VBN	denotes	hybridized
T10641	15616-15618	IN	denotes	to
T10642	15619-15623	RB	denotes	only
T10643	15650-15658	NN	denotes	fragment
T10644	15624-15625	DT	denotes	a
T10645	15626-15627	SYM	denotes	~
T10646	15627-15629	CD	denotes	16
T10647	15630-15632	NN	denotes	kb
T10648	15633-15637	NN	denotes	BglI
T10649	15638-15649	NN	denotes	restriction
T10650	15659-15661	IN	denotes	in
T10651	15662-15663	SYM	denotes	+
T10652	15664-15665	SYM	denotes	+
T10653	15663-15664	HYPH	denotes	/
T10654	15666-15670	NNS	denotes	mice
T10655	15670-15672	,	denotes	,
T10656	15672-15673	DT	denotes	a
T10657	15686-15694	NN	denotes	fragment
T10658	15674-15675	SYM	denotes	~
T10659	15675-15677	CD	denotes	11
T10660	15678-15680	NN	denotes	kb
T10661	15681-15685	NN	denotes	BglI
T10662	15695-15697	IN	denotes	in
T10663	15698-15699	SYM	denotes	-
T10664	15700-15701	SYM	denotes	-
T10665	15699-15700	HYPH	denotes	/
T10666	15702-15706	NNS	denotes	mice
T10667	15706-15708	,	denotes	,
T10668	15708-15711	CC	denotes	and
T10669	15712-15714	IN	denotes	to
T10670	15715-15719	DT	denotes	both
T10671	15720-15722	IN	denotes	of
T10672	15723-15728	DT	denotes	these
T10673	15729-15738	NNS	denotes	fragments
T10674	15739-15741	IN	denotes	in
T10675	15742-15743	SYM	denotes	+
T10676	15744-15745	SYM	denotes	-
T10677	15743-15744	HYPH	denotes	/
T10678	15746-15750	NNS	denotes	mice
T10679	15751-15752	-LRB-	denotes	(
T10680	15757-15759	NN	denotes	1B
T10681	15752-15756	NN	denotes	Fig.
T10682	15759-15760	-RRB-	denotes	)
T10683	15760-15761	.	denotes	.
T10684	15761-15834	sentence	denotes	Mice homozygous for the E2 mutation were born at the expected frequency.
T10685	15762-15766	NNS	denotes	Mice
T10686	15803-15807	VBN	denotes	born
T10687	15767-15777	JJ	denotes	homozygous
T10688	15778-15781	IN	denotes	for
T10689	15782-15785	DT	denotes	the
T10690	15789-15797	NN	denotes	mutation
T10691	15786-15788	NN	denotes	E2
T10692	15798-15802	VBD	denotes	were
T10693	15808-15810	IN	denotes	at
T10694	15811-15814	DT	denotes	the
T10695	15824-15833	NN	denotes	frequency
T10696	15815-15823	VBN	denotes	expected
T10697	15833-15834	.	denotes	.
T10698	15834-15982	sentence	denotes	Genotype analysis of pups derived from +/- by +/- matings revealed that +/+, +/-, and -/- mice were present at nearly the expected 1:2:1 frequency.
T10699	15835-15843	NN	denotes	Genotype
T10700	15844-15852	NN	denotes	analysis
T10701	15893-15901	VBD	denotes	revealed
T10702	15853-15855	IN	denotes	of
T10703	15856-15860	NNS	denotes	pups
T10704	15861-15868	VBN	denotes	derived
T10705	15869-15873	IN	denotes	from
T10706	15874-15875	SYM	denotes	+
T10707	15876-15877	SYM	denotes	-
T10708	15875-15876	HYPH	denotes	/
T10709	15885-15892	NNS	denotes	matings
T10710	15878-15880	IN	denotes	by
T10711	15881-15882	SYM	denotes	+
T10712	15883-15884	SYM	denotes	-
T10713	15882-15883	HYPH	denotes	/
T10714	15902-15906	IN	denotes	that
T10715	15930-15934	VBD	denotes	were
T10716	15907-15908	SYM	denotes	+
T10717	15909-15910	SYM	denotes	+
T10718	15908-15909	HYPH	denotes	/
T10719	15925-15929	NNS	denotes	mice
T10720	15910-15912	,	denotes	,
T10721	15912-15913	SYM	denotes	+
T10722	15914-15915	SYM	denotes	-
T10723	15913-15914	HYPH	denotes	/
T10724	15915-15917	,	denotes	,
T10725	15917-15920	CC	denotes	and
T10726	15921-15922	SYM	denotes	-
T10727	15923-15924	SYM	denotes	-
T10728	15922-15923	HYPH	denotes	/
T10729	15935-15942	JJ	denotes	present
T10730	15943-15945	IN	denotes	at
T10731	15946-15952	RB	denotes	nearly
T10732	15972-15981	NN	denotes	frequency
T10733	15953-15956	DT	denotes	the
T10734	15957-15965	VBN	denotes	expected
T10735	15966-15967	CD	denotes	1
T10736	15970-15971	CD	denotes	1
T10737	15967-15968	SYM	denotes	:
T10738	15968-15969	CD	denotes	2
T10739	15969-15970	SYM	denotes	:
T10740	15981-15982	.	denotes	.
T10741	15982-16080	sentence	denotes	Of the initial 60 animals genotyped, 19 (32%) were +/+, 27 (45%) were +/-, and 14 (23%) were -/-.
T10742	15983-15985	IN	denotes	Of
T10743	16029-16033	VBD	denotes	were
T10744	15986-15989	DT	denotes	the
T10745	16001-16008	NNS	denotes	animals
T10746	15990-15997	JJ	denotes	initial
T10747	15998-16000	CD	denotes	60
T10748	16009-16018	VBN	denotes	genotyped
T10749	16018-16020	,	denotes	,
T10750	16020-16022	CD	denotes	19
T10751	16023-16024	-LRB-	denotes	(
T10752	16026-16027	NN	denotes	%
T10753	16024-16026	CD	denotes	32
T10754	16027-16028	-RRB-	denotes	)
T10755	16034-16035	SYM	denotes	+
T10756	16036-16037	SYM	denotes	+
T10757	16035-16036	HYPH	denotes	/
T10758	16037-16039	,	denotes	,
T10759	16039-16041	CD	denotes	27
T10760	16048-16052	VBD	denotes	were
T10761	16042-16043	-LRB-	denotes	(
T10762	16045-16046	NN	denotes	%
T10763	16043-16045	CD	denotes	45
T10764	16046-16047	-RRB-	denotes	)
T10765	16053-16054	SYM	denotes	+
T10766	16055-16056	SYM	denotes	-
T10767	16054-16055	HYPH	denotes	/
T10768	16056-16058	,	denotes	,
T10769	16058-16061	CC	denotes	and
T10770	16062-16064	CD	denotes	14
T10771	16071-16075	VBD	denotes	were
T10772	16065-16066	-LRB-	denotes	(
T10773	16068-16069	NN	denotes	%
T10774	16066-16068	CD	denotes	23
T10775	16069-16070	-RRB-	denotes	)
T10776	16076-16077	SYM	denotes	-
T10777	16078-16079	SYM	denotes	-
T10778	16077-16078	HYPH	denotes	/
T10779	16079-16080	.	denotes	.
T10780	16080-16148	sentence	denotes	Thus, the E2 gene was dispensable for normal embryonic development.
T10781	16081-16085	RB	denotes	Thus
T10782	16099-16102	VBD	denotes	was
T10783	16085-16087	,	denotes	,
T10784	16087-16090	DT	denotes	the
T10785	16094-16098	NN	denotes	gene
T10786	16091-16093	NN	denotes	E2
T10787	16103-16114	JJ	denotes	dispensable
T10788	16115-16118	IN	denotes	for
T10789	16119-16125	JJ	denotes	normal
T10790	16136-16147	NN	denotes	development
T10791	16126-16135	JJ	denotes	embryonic
T10792	16147-16148	.	denotes	.
T10793	16148-16227	sentence	denotes	However, as expected, nearly all homozygous mice died in the perinatal period.
T10794	16149-16156	RB	denotes	However
T10795	16198-16202	VBD	denotes	died
T10796	16156-16158	,	denotes	,
T10797	16158-16160	IN	denotes	as
T10798	16161-16169	VBN	denotes	expected
T10799	16169-16171	,	denotes	,
T10800	16171-16177	RB	denotes	nearly
T10801	16193-16197	NNS	denotes	mice
T10802	16178-16181	DT	denotes	all
T10803	16182-16192	JJ	denotes	homozygous
T10804	16203-16205	IN	denotes	in
T10805	16206-16209	DT	denotes	the
T10806	16220-16226	NN	denotes	period
T10807	16210-16219	JJ	denotes	perinatal
T10808	16226-16227	.	denotes	.
T10809	16227-16378	sentence	denotes	Immediately following birth, homozygous pups were indistinguishable from their +/+ and +/- littermates; they were vigorous, active and able to suckle.
T10810	16228-16239	RB	denotes	Immediately
T10811	16240-16249	VBG	denotes	following
T10812	16273-16277	VBD	denotes	were
T10813	16250-16255	NN	denotes	birth
T10814	16255-16257	,	denotes	,
T10815	16257-16267	JJ	denotes	homozygous
T10816	16268-16272	NNS	denotes	pups
T10817	16337-16341	VBD	denotes	were
T10818	16278-16295	JJ	denotes	indistinguishable
T10819	16296-16300	IN	denotes	from
T10820	16301-16306	PRP$	denotes	their
T10821	16319-16330	NNS	denotes	littermates
T10822	16307-16308	SYM	denotes	+
T10823	16309-16310	SYM	denotes	+
T10824	16308-16309	HYPH	denotes	/
T10825	16311-16314	CC	denotes	and
T10826	16315-16316	SYM	denotes	+
T10827	16317-16318	SYM	denotes	-
T10828	16316-16317	HYPH	denotes	/
T10829	16330-16331	:	denotes	;
T10830	16332-16336	PRP	denotes	they
T10831	16342-16350	JJ	denotes	vigorous
T10832	16350-16352	,	denotes	,
T10833	16352-16358	JJ	denotes	active
T10834	16359-16362	CC	denotes	and
T10835	16363-16367	JJ	denotes	able
T10836	16368-16370	TO	denotes	to
T10837	16371-16377	VB	denotes	suckle
T10838	16377-16378	.	denotes	.
T10839	16378-16554	sentence	denotes	By mid to late day on postnatal day one, most -/- pups became moribund and were readily identifiable as they were lethargic, pale, and exhibited gasping respiratory movements.
T10840	16379-16381	IN	denotes	By
T10841	16434-16440	VBD	denotes	became
T10842	16382-16385	JJ	denotes	mid
T10843	16394-16397	NN	denotes	day
T10844	16386-16388	IN	denotes	to
T10845	16389-16393	JJ	denotes	late
T10846	16398-16400	IN	denotes	on
T10847	16401-16410	JJ	denotes	postnatal
T10848	16411-16414	NN	denotes	day
T10849	16415-16418	CD	denotes	one
T10850	16418-16420	,	denotes	,
T10851	16420-16424	RBS	denotes	most
T10852	16429-16433	NNS	denotes	pups
T10853	16425-16426	SYM	denotes	-
T10854	16427-16428	SYM	denotes	-
T10855	16426-16427	HYPH	denotes	/
T10856	16441-16449	JJ	denotes	moribund
T10857	16450-16453	CC	denotes	and
T10858	16454-16458	VBD	denotes	were
T10859	16459-16466	RB	denotes	readily
T10860	16467-16479	JJ	denotes	identifiable
T10861	16480-16482	IN	denotes	as
T10862	16488-16492	VBD	denotes	were
T10863	16483-16487	PRP	denotes	they
T10864	16493-16502	JJ	denotes	lethargic
T10865	16504-16508	JJ	denotes	pale
T10866	16502-16504	,	denotes	,
T10867	16508-16510	,	denotes	,
T10868	16510-16513	CC	denotes	and
T10869	16514-16523	VBD	denotes	exhibited
T10870	16524-16531	VBG	denotes	gasping
T10871	16544-16553	NNS	denotes	movements
T10872	16532-16543	JJ	denotes	respiratory
T10873	16553-16554	.	denotes	.
T10874	16554-16615	sentence	denotes	With few exceptions, -/- pups died within 72 hours of birth.
T10875	16555-16559	IN	denotes	With
T10876	16585-16589	VBD	denotes	died
T10877	16560-16563	JJ	denotes	few
T10878	16564-16574	NNS	denotes	exceptions
T10879	16574-16576	,	denotes	,
T10880	16576-16577	SYM	denotes	-
T10881	16578-16579	SYM	denotes	-
T10882	16577-16578	HYPH	denotes	/
T10883	16580-16584	NNS	denotes	pups
T10884	16590-16596	IN	denotes	within
T10885	16597-16599	CD	denotes	72
T10886	16600-16605	NNS	denotes	hours
T10887	16606-16608	IN	denotes	of
T10888	16609-16614	NN	denotes	birth
T10889	16614-16615	.	denotes	.
T10890	16615-16684	sentence	denotes	We have observed one rare -/- pup that survived to postnatal day 13.
T10891	16616-16618	PRP	denotes	We
T10892	16624-16632	VBN	denotes	observed
T10893	16619-16623	VBP	denotes	have
T10894	16633-16636	CD	denotes	one
T10895	16646-16649	NN	denotes	pup
T10896	16637-16641	JJ	denotes	rare
T10897	16642-16643	SYM	denotes	-
T10898	16644-16645	SYM	denotes	-
T10899	16643-16644	HYPH	denotes	/
T10900	16650-16654	WDT	denotes	that
T10901	16655-16663	VBD	denotes	survived
T10902	16664-16666	IN	denotes	to
T10903	16667-16676	JJ	denotes	postnatal
T10904	16677-16680	NN	denotes	day
T10905	16681-16683	CD	denotes	13
T10906	16683-16684	.	denotes	.
T10907	16684-16746	sentence	denotes	The reason for the prolonged survival of this pup is unknown.
T10908	16685-16688	DT	denotes	The
T10909	16689-16695	NN	denotes	reason
T10910	16735-16737	VBZ	denotes	is
T10911	16696-16699	IN	denotes	for
T10912	16700-16703	DT	denotes	the
T10913	16714-16722	NN	denotes	survival
T10914	16704-16713	VBN	denotes	prolonged
T10915	16723-16725	IN	denotes	of
T10916	16726-16730	DT	denotes	this
T10917	16731-16734	NN	denotes	pup
T10918	16738-16745	JJ	denotes	unknown
T10919	16745-16746	.	denotes	.
T12206	16748-16750	NN	denotes	E2
T12207	16751-16760	JJ	denotes	deficient
T12208	16761-16765	NNS	denotes	mice
T12209	16777-16782	VBP	denotes	model
T12210	16766-16776	RB	denotes	accurately
T12211	16783-16790	JJ	denotes	classic
T12212	16791-16795	NN	denotes	MSUD
T12213	16795-16989	sentence	denotes	To demonstrate that the gene targeting event created a true E2 null allele, we determined BCKDH activity in liver homogenates of postnatal day 1 mouse pups derived from +/- by +/- mating pairs.
T12214	16796-16798	TO	denotes	To
T12215	16799-16810	VB	denotes	demonstrate
T12216	16875-16885	VBD	denotes	determined
T12217	16811-16815	IN	denotes	that
T12218	16841-16848	VBD	denotes	created
T12219	16816-16819	DT	denotes	the
T12220	16835-16840	NN	denotes	event
T12221	16820-16824	NN	denotes	gene
T12222	16825-16834	NN	denotes	targeting
T12223	16849-16850	DT	denotes	a
T12224	16864-16870	NN	denotes	allele
T12225	16851-16855	JJ	denotes	true
T12226	16856-16858	NN	denotes	E2
T12227	16859-16863	JJ	denotes	null
T12228	16870-16872	,	denotes	,
T12229	16872-16874	PRP	denotes	we
T12230	16886-16891	NN	denotes	BCKDH
T12231	16892-16900	NN	denotes	activity
T12232	16901-16903	IN	denotes	in
T12233	16904-16909	NN	denotes	liver
T12234	16910-16921	NNS	denotes	homogenates
T12235	16922-16924	IN	denotes	of
T12236	16925-16934	JJ	denotes	postnatal
T12237	16935-16938	NN	denotes	day
T12238	16947-16951	NNS	denotes	pups
T12239	16939-16940	CD	denotes	1
T12247	16969-16971	IN	denotes	by
T12248	16972-16973	SYM	denotes	+
T12249	16974-16975	SYM	denotes	-
T12250	16973-16974	HYPH	denotes	/
T12251	16976-16982	NN	denotes	mating
T12252	16988-16989	.	denotes	.
T12253	16989-17067	sentence	denotes	As shown in Figure 2A, the BCKDH activity in +/+ mice was readily detectable.
T12254	16990-16992	IN	denotes	As
T12255	16993-16998	VBN	denotes	shown
T12256	17044-17047	VBD	denotes	was
T12257	16999-17001	IN	denotes	in
T12258	17002-17008	NN	denotes	Figure
T12259	17009-17011	NN	denotes	2A
T12260	17011-17013	,	denotes	,
T12261	17013-17016	DT	denotes	the
T12262	17023-17031	NN	denotes	activity
T12263	17017-17022	NN	denotes	BCKDH
T12264	17032-17034	IN	denotes	in
T12265	17035-17036	SYM	denotes	+
T12266	17037-17038	SYM	denotes	+
T12267	17036-17037	HYPH	denotes	/
T12268	17039-17043	NNS	denotes	mice
T12269	17048-17055	RB	denotes	readily
T12270	17056-17066	JJ	denotes	detectable
T12271	17066-17067	.	denotes	.
T12272	17067-17145	sentence	denotes	In marked contrast, BCKDH activity was completely absent in -/- mouse livers.
T12273	17068-17070	IN	denotes	In
T12274	17103-17106	VBD	denotes	was
T12275	17071-17077	JJ	denotes	marked
T12276	17078-17086	NN	denotes	contrast
T12277	17086-17088	,	denotes	,
T12278	17088-17093	NN	denotes	BCKDH
T12279	17094-17102	NN	denotes	activity
T12280	17107-17117	RB	denotes	completely
T12281	17118-17124	JJ	denotes	absent
T12282	17125-17127	IN	denotes	in
T12283	17128-17129	SYM	denotes	-
T12284	17130-17131	SYM	denotes	-
T12285	17129-17130	HYPH	denotes	/
T12286	17138-17144	NNS	denotes	livers
T12287	17132-17137	NN	denotes	mouse
T12288	17144-17145	.	denotes	.
T12289	17145-17258	sentence	denotes	As expected, homogenates from +/- mice had approximately half the activity of their +/+ littermates (Figure 2A).
T12290	17146-17148	IN	denotes	As
T12291	17149-17157	VBN	denotes	expected
T12292	17185-17188	VBD	denotes	had
T12293	17157-17159	,	denotes	,
T12294	17159-17170	NNS	denotes	homogenates
T12295	17171-17175	IN	denotes	from
T12296	17176-17177	SYM	denotes	+
T12297	17178-17179	SYM	denotes	-
T12298	17177-17178	HYPH	denotes	/
T12299	17180-17184	NNS	denotes	mice
T12300	17189-17202	RB	denotes	approximately
T12301	17203-17207	PDT	denotes	half
T12302	17212-17220	NN	denotes	activity
T12303	17208-17211	DT	denotes	the
T12304	17221-17223	IN	denotes	of
T12305	17224-17229	PRP$	denotes	their
T12306	17234-17245	NNS	denotes	littermates
T12307	17230-17231	SYM	denotes	+
T12308	17232-17233	SYM	denotes	+
T12309	17231-17232	HYPH	denotes	/
T12310	17246-17247	-LRB-	denotes	(
T12311	17254-17256	NN	denotes	2A
T12312	17247-17253	NN	denotes	Figure
T12313	17256-17257	-RRB-	denotes	)
T12314	17257-17258	.	denotes	.
T12315	17258-17346	sentence	denotes	The results from -/- mice are similar to that observed in humans with classic MSUD [1].
T12316	17259-17262	DT	denotes	The
T12317	17263-17270	NNS	denotes	results
T12318	17285-17288	VBP	denotes	are
T12319	17271-17275	IN	denotes	from
T12320	17276-17277	SYM	denotes	-
T12321	17278-17279	SYM	denotes	-
T12322	17277-17278	HYPH	denotes	/
T12323	17280-17284	NNS	denotes	mice
T12324	17289-17296	JJ	denotes	similar
T12325	17297-17299	IN	denotes	to
T12326	17300-17304	DT	denotes	that
T12327	17305-17313	VBN	denotes	observed
T12328	17314-17316	IN	denotes	in
T12329	17317-17323	NNS	denotes	humans
T12330	17324-17328	IN	denotes	with
T12331	17329-17336	JJ	denotes	classic
T12332	17337-17341	NN	denotes	MSUD
T12333	17342-17343	-LRB-	denotes	[
T12334	17343-17344	CD	denotes	1
T12335	17344-17345	-RRB-	denotes	]
T12336	17345-17346	.	denotes	.
T12337	17346-17347	sentence	denotes
T12346	18235-18238	VBD	denotes	was
T12347	18244-18246	TO	denotes	to
T12348	18247-18254	VB	denotes	examine
T12349	18255-18257	NN	denotes	E2
T12350	18258-18265	NN	denotes	protein
T12351	18266-18268	IN	denotes	in
T12352	18269-18272	DT	denotes	the
T12353	18273-18277	NNS	denotes	mice
T12354	18277-18278	.	denotes	.
T12355	18278-18394	sentence	denotes	As shown in Figure 1C and 1D, immunoreactive E2 protein was abundant in liver and embryonic fibroblasts of+/+ mice.
T12356	18279-18281	IN	denotes	As
T12357	18282-18287	VBN	denotes	shown
T12358	18335-18338	VBD	denotes	was
T12359	18288-18290	IN	denotes	in
T12360	18291-18297	NN	denotes	Figure
T12361	18298-18300	NN	denotes	1C
T12362	18301-18304	CC	denotes	and
T12363	18305-18307	NN	denotes	1D
T12364	18307-18309	,	denotes	,
T12365	18309-18323	JJ	denotes	immunoreactive
T12366	18327-18334	NN	denotes	protein
T12367	18324-18326	NN	denotes	E2
T12368	18339-18347	JJ	denotes	abundant
T12369	18348-18350	IN	denotes	in
T12370	18351-18356	NN	denotes	liver
T12371	18357-18360	CC	denotes	and
T12372	18361-18370	JJ	denotes	embryonic
T12373	18371-18382	NNS	denotes	fibroblasts
T12374	18383-18385	IN	denotes	of
T12375	18385-18386	SYM	denotes	+
T12376	18387-18388	SYM	denotes	+
T12377	18386-18387	HYPH	denotes	/
T12378	18389-18393	NNS	denotes	mice
T12379	18393-18394	.	denotes	.
T12380	18394-18486	sentence	denotes	In marked contrast, immunoreactive E2 protein was absent in these same tissues of -/- mice.
T12381	18395-18397	IN	denotes	In
T12382	18441-18444	VBD	denotes	was
T12383	18398-18404	JJ	denotes	marked
T12384	18405-18413	NN	denotes	contrast
T12385	18413-18415	,	denotes	,
T12386	18415-18429	JJ	denotes	immunoreactive
T12387	18433-18440	NN	denotes	protein
T12388	18430-18432	NN	denotes	E2
T12389	18445-18451	JJ	denotes	absent
T12390	18452-18454	IN	denotes	in
T12391	18455-18460	DT	denotes	these
T12392	18466-18473	NNS	denotes	tissues
T12393	18461-18465	JJ	denotes	same
T12394	18474-18476	IN	denotes	of
T12395	18477-18478	SYM	denotes	-
T12396	18479-18480	SYM	denotes	-
T12397	18478-18479	HYPH	denotes	/
T12398	18481-18485	NNS	denotes	mice
T12399	18485-18486	.	denotes	.
T12400	18486-18685	sentence	denotes	Homozygous E2 knockout mice had a nearly 3-fold increase in blood (Figure 2B) and urine (data not shown) levels of BCAA (sum of leucine, isoleucine, and valine) as compared to their +/+ littermates.
T12401	18487-18497	JJ	denotes	Homozygous
T12402	18501-18509	NN	denotes	knockout
T12403	18498-18500	NN	denotes	E2
T12404	18510-18514	NNS	denotes	mice
T12405	18515-18518	VBD	denotes	had
T12406	18519-18520	DT	denotes	a
T12407	18535-18543	NN	denotes	increase
T12408	18521-18527	RB	denotes	nearly
T12409	18528-18529	CD	denotes	3
T12410	18530-18534	JJ	denotes	fold
T12411	18529-18530	HYPH	denotes	-
T12412	18544-18546	IN	denotes	in
T12413	18547-18552	NN	denotes	blood
T12414	18592-18598	NNS	denotes	levels
T12415	18553-18554	-LRB-	denotes	(
T12416	18561-18563	NN	denotes	2B
T12417	18554-18560	NN	denotes	Figure
T12418	18563-18564	-RRB-	denotes	)
T12419	18565-18568	CC	denotes	and
T12420	18569-18574	NN	denotes	urine
T12421	18575-18576	-LRB-	denotes	(
T12422	18585-18590	VBN	denotes	shown
T12423	18576-18580	NNS	denotes	data
T12424	18581-18584	RB	denotes	not
T12425	18590-18591	-RRB-	denotes	)
T12426	18599-18601	IN	denotes	of
T12427	18602-18606	NN	denotes	BCAA
T12428	18607-18608	-LRB-	denotes	(
T12429	18608-18611	NN	denotes	sum
T12430	18612-18614	IN	denotes	of
T12431	18615-18622	NN	denotes	leucine
T12432	18622-18624	,	denotes	,
T12433	18624-18634	NN	denotes	isoleucine
T12434	18634-18636	,	denotes	,
T12435	18636-18639	CC	denotes	and
T12436	18640-18646	NN	denotes	valine
T12437	18646-18647	-RRB-	denotes	)
T12438	18648-18650	IN	denotes	as
T12439	18651-18659	VBN	denotes	compared
T12440	18660-18662	IN	denotes	to
T12441	18663-18668	PRP$	denotes	their
T12442	18673-18684	NNS	denotes	littermates
T12443	18669-18670	SYM	denotes	+
T12444	18671-18672	SYM	denotes	+
T12445	18670-18671	HYPH	denotes	/
T12446	18684-18685	.	denotes	.
T12447	18685-18861	sentence	denotes	Because amino acids were analyzed by tandem mass spectrometry, the sum of BCAA shown in Figure 2B also may include alloisoleucine that may have been produced in -/- MSUD mice.
T12448	18686-18693	IN	denotes	Because
T12449	18711-18719	VBN	denotes	analyzed
T12450	18694-18699	NN	denotes	amino
T12451	18700-18705	NNS	denotes	acids
T12452	18706-18710	VBD	denotes	were
T12453	18793-18800	VB	denotes	include
T12454	18720-18722	IN	denotes	by
T12455	18723-18729	NN	denotes	tandem
T12456	18735-18747	NN	denotes	spectrometry
T12457	18730-18734	NN	denotes	mass
T12458	18747-18749	,	denotes	,
T12459	18749-18752	DT	denotes	the
T12460	18753-18756	NN	denotes	sum
T12461	18757-18759	IN	denotes	of
T12462	18760-18764	NN	denotes	BCAA
T12463	18765-18770	VBN	denotes	shown
T12464	18771-18773	IN	denotes	in
T12465	18774-18780	NN	denotes	Figure
T12466	18781-18783	NN	denotes	2B
T12467	18784-18788	RB	denotes	also
T12468	18789-18792	MD	denotes	may
T12469	18801-18815	NN	denotes	alloisoleucine
T12470	18816-18820	WDT	denotes	that
T12471	18835-18843	VBN	denotes	produced
T12472	18821-18824	MD	denotes	may
T12473	18825-18829	VB	denotes	have
T12474	18830-18834	VBN	denotes	been
T12475	18844-18846	IN	denotes	in
T12476	18847-18848	SYM	denotes	-
T12477	18849-18850	SYM	denotes	-
T12478	18848-18849	HYPH	denotes	/
T12479	18856-18860	NNS	denotes	mice
T12480	18851-18855	NN	denotes	MSUD
T12481	18860-18861	.	denotes	.
T12482	18861-18956	sentence	denotes	The metabolism of BCAA is linked with the synthesis of alanine, glutamate, and glutamine [33].
T12483	18862-18865	DT	denotes	The
T12484	18866-18876	NN	denotes	metabolism
T12485	18888-18894	VBN	denotes	linked
T12486	18877-18879	IN	denotes	of
T12487	18880-18884	NN	denotes	BCAA
T12488	18885-18887	VBZ	denotes	is
T12489	18895-18899	IN	denotes	with
T12490	18900-18903	DT	denotes	the
T12491	18904-18913	NN	denotes	synthesis
T12492	18914-18916	IN	denotes	of
T12493	18917-18924	NN	denotes	alanine
T12494	18924-18926	,	denotes	,
T12495	18926-18935	NN	denotes	glutamate
T12496	18935-18937	,	denotes	,
T12497	18937-18940	CC	denotes	and
T12498	18941-18950	NN	denotes	glutamine
T12499	18951-18952	-LRB-	denotes	[
T12500	18952-18954	CD	denotes	33
T12501	18954-18955	-RRB-	denotes	]
T12502	18955-18956	.	denotes	.
T12503	18956-19149	sentence	denotes	Because of impaired metabolism of BCAA in MSUD mice, and to further characterize the abnormal biochemistry in this model, we analyzed the blood levels of the alanine, glutamate, and glutamine.
T12504	18957-18964	IN	denotes	Because
T12505	19082-19090	VBD	denotes	analyzed
T12506	18965-18967	IN	denotes	of
T12507	18968-18976	JJ	denotes	impaired
T12508	18977-18987	NN	denotes	metabolism
T12509	18988-18990	IN	denotes	of
T12510	18991-18995	NN	denotes	BCAA
T12511	18996-18998	IN	denotes	in
T12512	18999-19003	NN	denotes	MSUD
T12513	19004-19008	NNS	denotes	mice
T12514	19008-19010	,	denotes	,
T12515	19010-19013	CC	denotes	and
T12516	19014-19016	TO	denotes	to
T12517	19025-19037	VB	denotes	characterize
T12518	19017-19024	RB	denotes	further
T12519	19038-19041	DT	denotes	the
T12520	19051-19063	NN	denotes	biochemistry
T12521	19042-19050	JJ	denotes	abnormal
T12522	19064-19066	IN	denotes	in
T12523	19067-19071	DT	denotes	this
T12524	19072-19077	NN	denotes	model
T12525	19077-19079	,	denotes	,
T12526	19079-19081	PRP	denotes	we
T12527	19091-19094	DT	denotes	the
T12528	19101-19107	NNS	denotes	levels
T12529	19095-19100	NN	denotes	blood
T12530	19108-19110	IN	denotes	of
T12531	19111-19114	DT	denotes	the
T12532	19115-19122	NN	denotes	alanine
T12533	19122-19124	,	denotes	,
T12534	19124-19133	NN	denotes	glutamate
T12535	19133-19135	,	denotes	,
T12536	19135-19138	CC	denotes	and
T12537	19139-19148	NN	denotes	glutamine
T12538	19148-19149	.	denotes	.
T12539	19149-19281	sentence	denotes	As shown in Table 1, the levels of all three amino acids in homozygous mice were markedly lower than the levels in +/+ or +/- mice.
T12540	19150-19152	IN	denotes	As
T12541	19153-19158	VBN	denotes	shown
T12542	19226-19230	VBD	denotes	were
T12543	19159-19161	IN	denotes	in
T12544	19162-19167	NN	denotes	Table
T12545	19168-19169	CD	denotes	1
T12546	19169-19171	,	denotes	,
T12547	19171-19174	DT	denotes	the
T12548	19175-19181	NNS	denotes	levels
T12549	19182-19184	IN	denotes	of
T12550	19185-19188	DT	denotes	all
T12551	19201-19206	NNS	denotes	acids
T12552	19189-19194	CD	denotes	three
T12553	19195-19200	NN	denotes	amino
T12554	19207-19209	IN	denotes	in
T12555	19210-19220	JJ	denotes	homozygous
T12556	19221-19225	NNS	denotes	mice
T12557	19231-19239	RB	denotes	markedly
T12558	19240-19245	JJR	denotes	lower
T12559	19246-19250	IN	denotes	than
T12560	19251-19254	DT	denotes	the
T12561	19255-19261	NNS	denotes	levels
T12562	19262-19264	IN	denotes	in
T12563	19265-19266	SYM	denotes	+
T12564	19267-19268	SYM	denotes	+
T12565	19266-19267	HYPH	denotes	/
T12566	19276-19280	NNS	denotes	mice
T12567	19269-19271	CC	denotes	or
T12568	19272-19273	SYM	denotes	+
T12569	19274-19275	SYM	denotes	-
T12570	19273-19274	HYPH	denotes	/
T12571	19280-19281	.	denotes	.
T12572	19281-19377	sentence	denotes	The levels of these amino acids in the +/- mice were comparable to those in +/+ mice (Table 1).
T12573	19282-19285	DT	denotes	The
T12574	19286-19292	NNS	denotes	levels
T12575	19330-19334	VBD	denotes	were
T12576	19293-19295	IN	denotes	of
T12577	19296-19301	DT	denotes	these
T12578	19308-19313	NNS	denotes	acids
T12579	19302-19307	NN	denotes	amino
T12580	19314-19316	IN	denotes	in
T12581	19317-19320	DT	denotes	the
T12582	19325-19329	NNS	denotes	mice
T12583	19321-19322	SYM	denotes	+
T12584	19323-19324	SYM	denotes	-
T12585	19322-19323	HYPH	denotes	/
T12586	19335-19345	JJ	denotes	comparable
T12587	19346-19348	IN	denotes	to
T12588	19349-19354	DT	denotes	those
T12589	19355-19357	IN	denotes	in
T12590	19358-19359	SYM	denotes	+
T12591	19360-19361	SYM	denotes	+
T12592	19359-19360	HYPH	denotes	/
T12593	19362-19366	NNS	denotes	mice
T12594	19367-19368	-LRB-	denotes	(
T12595	19368-19373	NN	denotes	Table
T12596	19374-19375	CD	denotes	1
T12597	19375-19376	-RRB-	denotes	)
T12598	19376-19377	.	denotes	.
T12599	19377-19683	sentence	denotes	Because of the abnormal decrease in the blood alanine level and marked rise in blood BCAA levels that are characteristic of MSUD, a recent report on MSUD patients has suggested that the ratio of BCAA/alanine provides a more sensitive measure of the abnormal biochemistry of MSUD than BCAA level alone [8].
T12600	19378-19385	IN	denotes	Because
T12601	19545-19554	VBN	denotes	suggested
T12602	19386-19388	IN	denotes	of
T12603	19389-19392	DT	denotes	the
T12604	19402-19410	NN	denotes	decrease
T12605	19393-19401	JJ	denotes	abnormal
T12606	19411-19413	IN	denotes	in
T12607	19414-19417	DT	denotes	the
T12608	19432-19437	NN	denotes	level
T12609	19418-19423	NN	denotes	blood
T12610	19424-19431	NN	denotes	alanine
T12611	19438-19441	CC	denotes	and
T12612	19442-19448	JJ	denotes	marked
T12613	19449-19453	NN	denotes	rise
T12614	19454-19456	IN	denotes	in
T12615	19457-19462	NN	denotes	blood
T12616	19468-19474	NNS	denotes	levels
T12617	19463-19467	NN	denotes	BCAA
T12618	19475-19479	WDT	denotes	that
T12619	19480-19483	VBP	denotes	are
T12620	19484-19498	JJ	denotes	characteristic
T12621	19499-19501	IN	denotes	of
T12622	19502-19506	NN	denotes	MSUD
T12623	19506-19508	,	denotes	,
T12624	19508-19509	DT	denotes	a
T12625	19517-19523	NN	denotes	report
T12626	19510-19516	JJ	denotes	recent
T12627	19524-19526	IN	denotes	on
T12628	19527-19531	NN	denotes	MSUD
T12629	19532-19540	NNS	denotes	patients
T12630	19541-19544	VBZ	denotes	has
T12631	19555-19559	IN	denotes	that
T12632	19586-19594	VBZ	denotes	provides
T12633	19560-19563	DT	denotes	the
T12634	19564-19569	NN	denotes	ratio
T12635	19570-19572	IN	denotes	of
T12636	19573-19577	NN	denotes	BCAA
T12637	19578-19585	NN	denotes	alanine
T12638	19577-19578	HYPH	denotes	/
T12639	19595-19596	DT	denotes	a
T12640	19612-19619	NN	denotes	measure
T12641	19597-19601	RBR	denotes	more
T12642	19602-19611	JJ	denotes	sensitive
T12643	19620-19622	IN	denotes	of
T12644	19623-19626	DT	denotes	the
T12645	19636-19648	NN	denotes	biochemistry
T12646	19627-19635	JJ	denotes	abnormal
T12647	19649-19651	IN	denotes	of
T12648	19652-19656	NN	denotes	MSUD
T12649	19657-19661	IN	denotes	than
T12650	19662-19666	NN	denotes	BCAA
T12651	19667-19672	NN	denotes	level
T12652	19673-19678	RB	denotes	alone
T12653	19679-19680	-LRB-	denotes	[
T12654	19680-19681	CD	denotes	8
T12655	19681-19682	-RRB-	denotes	]
T12656	19682-19683	.	denotes	.
T12657	19683-19758	sentence	denotes	Therefore, we also expressed the amino acid results as BCAA/alanine ratio.
T12658	19684-19693	RB	denotes	Therefore
T12659	19703-19712	VBD	denotes	expressed
T12660	19693-19695	,	denotes	,
T12661	19695-19697	PRP	denotes	we
T12662	19698-19702	RB	denotes	also
T12701	19847-19848	SYM	denotes	-
T12702	19846-19847	HYPH	denotes	/
T12703	19860-19861	.	denotes	.
T12704	19861-19968	sentence	denotes	These blood amino acid results are consistent with the concentrations seen in patients with MSUD [1,8,15].
T12705	19862-19867	DT	denotes	These
T12706	19885-19892	NNS	denotes	results
T12707	19868-19873	NN	denotes	blood
T12708	19874-19879	NN	denotes	amino
T12709	19880-19884	NN	denotes	acid
T12710	19893-19896	VBP	denotes	are
T12711	19897-19907	JJ	denotes	consistent
T12712	19908-19912	IN	denotes	with
T12713	19913-19916	DT	denotes	the
T12714	19917-19931	NNS	denotes	concentrations
T12715	19932-19936	VBN	denotes	seen
T12716	19937-19939	IN	denotes	in
T12717	19940-19948	NNS	denotes	patients
T12718	19949-19953	IN	denotes	with
T12719	19954-19958	NN	denotes	MSUD
T12720	19959-19960	-LRB-	denotes	[
T12721	19964-19966	CD	denotes	15
T12722	19960-19961	CD	denotes	1
T12723	19961-19962	,	denotes	,
T12724	19962-19963	CD	denotes	8
T12725	19963-19964	,	denotes	,
T12726	19966-19967	-RRB-	denotes	]
T12727	19967-19968	.	denotes	.
T17015	30149-30155	JJ	denotes	useful
T21164	37334-37335	.	denotes	.
T21163	37327-37334	NNS	denotes	enzymes
T21162	37314-37326	JJ	denotes	multisubunit
T21161	37311-37313	IN	denotes	in
T21160	37303-37310	NNS	denotes	defects
T21159	37300-37302	IN	denotes	to
T21158	37296-37299	IN	denotes	due
T21157	37272-37285	JJ	denotes	mitochondrial
T21156	37286-37295	NNS	denotes	disorders
T21155	37266-37271	JJ	denotes	other
T21154	37263-37265	IN	denotes	to
T21153	37250-37262	JJ	denotes	transferable
T21152	37246-37249	CC	denotes	and
T21151	37235-37245	JJ	denotes	applicable
T21150	37227-37231	RB	denotes	also
T21149	37222-37226	MD	denotes	will
T21148	37217-37221	RB	denotes	here
T21147	37207-37216	VBN	denotes	described
T21146	37195-37199	NN	denotes	MSUD
T21145	37200-37206	NNS	denotes	models
T21144	37191-37194	DT	denotes	the
T21143	37186-37190	IN	denotes	with
T21142	37178-37185	NNS	denotes	studies
T21141	37173-37177	IN	denotes	from
T21140	37166-37172	VBN	denotes	gained
T21139	37156-37165	NN	denotes	knowledge
T21138	37152-37155	CC	denotes	and
T21137	37140-37151	NN	denotes	information
T21136	37136-37139	DT	denotes	the
T21135	37134-37136	,	denotes	,
T21134	37232-37234	VB	denotes	be
T21133	37128-37134	RB	denotes	Lastly
T21132	37127-37335	sentence	denotes	Lastly, the information and knowledge gained from studies with the MSUD models described here will also be applicable and transferable to other mitochondrial disorders due to defects in multisubunit enzymes.
T21131	37126-37127	.	denotes	.
T21130	37119-37126	NN	denotes	biology
T21129	37108-37118	JJ	denotes	structural
T21128	37105-37107	IN	denotes	of
T21127	37097-37104	NNS	denotes	studies
T21126	37093-37096	IN	denotes	for
T21125	37075-37083	JJ	denotes	valuable
T21124	37084-37092	NN	denotes	resource
T21123	37073-37074	DT	denotes	a
T21122	37061-37064	MD	denotes	may
T21328	37585-37587	RB	denotes	as
T21327	37583-37585	,	denotes	,
T21326	37579-37583	NN	denotes	MSUD
T21325	37576-37578	IN	denotes	of
T21324	37563-37575	NN	denotes	pathogenesis
T21323	37559-37562	DT	denotes	the
T21322	37538-37545	RB	denotes	further
T21321	37546-37558	VB	denotes	characterize
T21320	37535-37537	TO	denotes	to
T21319	37528-37534	NNS	denotes	models
T21318	37521-37527	JJ	denotes	useful
T21317	37513-37520	VBP	denotes	provide
T21316	37505-37512	NNS	denotes	animals
T21315	37499-37504	DT	denotes	These
T21314	37498-37722	sentence	denotes	These animals provide useful models to further characterize the pathogenesis of MSUD, as well as models to test novel therapeutic strategies, such as gene and cellular therapies, to treat this devastating metabolic disease.
T21313	37497-37498	.	denotes	.
T21312	37480-37492	JJ	denotes	intermediate
T21311	37472-37476	RB	denotes	well
T21310	37477-37479	IN	denotes	as
T21309	37469-37471	RB	denotes	as
T21308	37493-37497	NN	denotes	MSUD
T21307	37461-37468	JJ	denotes	classic
T21306	37458-37460	IN	denotes	of
T21305	37445-37450	NN	denotes	mouse
T21304	37451-37457	NNS	denotes	models
T21303	37434-37444	VBN	denotes	engineered
T21302	37422-37433	RB	denotes	genetically
T21301	37419-37421	IN	denotes	of
T21300	37402-37418	NN	denotes	characterization
T21299	37398-37401	CC	denotes	and
T21298	37386-37397	NN	denotes	development
T21297	37382-37385	DT	denotes	the
T21296	37365-37371	NN	denotes	report
T21295	37360-37364	DT	denotes	this
T21294	37358-37360	,	denotes	,
T21293	37351-37358	NN	denotes	summary
T21292	37372-37381	VBZ	denotes	describes
T21291	37348-37350	IN	denotes	In
T21332	37603-37605	TO	denotes	to
T21331	37596-37602	NNS	denotes	models
T21330	37588-37592	RB	denotes	well
T21329	37593-37595	IN	denotes	as
T21383	38773-38774	:	denotes	:
T21382	38769-38773	RB	denotes	here
T21381	38757-38759	VB	denotes	be
T21380	38753-38756	MD	denotes	can
T21379	38747-38752	NN	denotes	paper
T21378	38742-38746	DT	denotes	this
T21377	38738-38741	IN	denotes	for
T21376	38760-38768	VBN	denotes	accessed
T21375	38714-38729	JJ	denotes	pre-publication
T21374	38730-38737	NN	denotes	history
T21373	38710-38713	DT	denotes	The
T21351	37721-37722	.	denotes	.
T21350	37704-37713	JJ	denotes	metabolic
T21349	37692-37703	VBG	denotes	devastating
T21348	37714-37721	NN	denotes	disease
T21347	37687-37691	DT	denotes	this
T21346	37681-37686	VB	denotes	treat
T21345	37678-37680	TO	denotes	to
T21344	37676-37678	,	denotes	,
T21343	37658-37666	JJ	denotes	cellular
T21342	37654-37657	CC	denotes	and
T21341	37667-37676	NNS	denotes	therapies
T22055	6693-6695	NN	denotes	E2
T22056	6716-6726	NN	denotes	production
T22057	6696-6700	NN	denotes	gene
T22058	6701-6709	NN	denotes	knockout
T22059	6710-6715	NN	denotes	mouse
T22060	6726-6727	.	denotes	.
T22061	6727-6805	sentence	denotes	A, Gene targeting strategy used for targeting the E2 locus in mouse ES cells.
T22062	6728-6729	LS	denotes	A
T22063	6746-6754	NN	denotes	strategy
T22064	6729-6731	,	denotes	,
T22065	6731-6735	NN	denotes	Gene
T22066	6736-6745	NN	denotes	targeting
T22067	6755-6759	VBN	denotes	used
T22068	6760-6763	IN	denotes	for
T22069	6764-6773	VBG	denotes	targeting
T22070	6774-6777	DT	denotes	the
T22071	6781-6786	NN	denotes	locus
T22072	6778-6780	NN	denotes	E2
T22073	6787-6789	IN	denotes	in
T22074	6790-6795	NN	denotes	mouse
T22075	6799-6804	NNS	denotes	cells
T22076	6796-6798	NN	denotes	ES
T22077	6804-6805	.	denotes	.
T22078	6805-6933	sentence	denotes	The targeting construct was designed to delete 1.67 kb of sequence between an EcoRV site in Exon 4 and a Smal site in intron 5.
T22079	6806-6809	DT	denotes	The
T22080	6820-6829	NN	denotes	construct
T22081	6810-6819	NN	denotes	targeting
T22082	6834-6842	VBN	denotes	designed
T22083	6830-6833	VBD	denotes	was
T22084	6843-6845	TO	denotes	to
T22085	6846-6852	VB	denotes	delete
T22086	6853-6857	CD	denotes	1.67
T22087	6858-6860	NN	denotes	kb
T22088	6861-6863	IN	denotes	of
T22089	6864-6872	NN	denotes	sequence
T22090	6873-6880	IN	denotes	between
T22091	6881-6883	DT	denotes	an
T22092	6890-6894	NN	denotes	site
T22093	6884-6889	NN	denotes	EcoRV
T22094	6895-6897	IN	denotes	in
T22095	6898-6902	NN	denotes	Exon
T22096	6903-6904	CD	denotes	4
T22097	6905-6908	CC	denotes	and
T22098	6909-6910	DT	denotes	a
T22099	6916-6920	NN	denotes	site
T22100	6911-6915	NN	denotes	Smal
T22101	6921-6923	IN	denotes	in
T22102	6924-6930	NN	denotes	intron
T22103	6931-6932	CD	denotes	5
T22104	6932-6933	.	denotes	.
T22105	6933-7046	sentence	denotes	The wild type E2 gene contains an ~16 kb BglI restriction fragment that hybridizes to the Exon 6 specific probe.
T22106	6934-6937	DT	denotes	The
T22107	6951-6955	NN	denotes	gene
T22108	6938-6942	JJ	denotes	wild
T22109	6943-6947	NN	denotes	type
T22110	6948-6950	NN	denotes	E2
T22111	6956-6964	VBZ	denotes	contains
T22112	6965-6967	DT	denotes	an
T22113	6992-7000	NN	denotes	fragment
T22114	6968-6969	SYM	denotes	~
T22115	6969-6971	CD	denotes	16
T22116	6972-6974	NN	denotes	kb
T22117	6975-6979	NN	denotes	BglI
T22118	6980-6991	NN	denotes	restriction
T22119	7001-7005	WDT	denotes	that
T22120	7006-7016	VBZ	denotes	hybridizes
T22121	7017-7019	IN	denotes	to
T22122	7020-7023	DT	denotes	the
T22123	7040-7045	NN	denotes	probe
T22124	7024-7028	NN	denotes	Exon
T22125	7031-7039	JJ	denotes	specific
T22126	7029-7030	CD	denotes	6
T22127	7045-7046	.	denotes	.
T22128	7046-7155	sentence	denotes	A correctly targeted E2 locus harbors an ~11 kb BglI restriction fragment that hybridizes to the same probe.
T22129	7047-7048	DT	denotes	A
T22130	7071-7076	NN	denotes	locus
T22131	7049-7058	RB	denotes	correctly
T22132	7059-7067	VBN	denotes	targeted
T22133	7068-7070	NN	denotes	E2
T22134	7077-7084	VBZ	denotes	harbors
T22135	7085-7087	DT	denotes	an
T22136	7112-7120	NN	denotes	fragment
T22137	7088-7089	SYM	denotes	~
T22138	7089-7091	CD	denotes	11
T22139	7092-7094	NN	denotes	kb
T22140	7095-7099	NN	denotes	BglI
T22141	7100-7111	NN	denotes	restriction
T22142	7121-7125	WDT	denotes	that
T22143	7126-7136	VBZ	denotes	hybridizes
T22144	7137-7139	IN	denotes	to
T22145	7140-7143	DT	denotes	the
T22146	7149-7154	NN	denotes	probe
T22147	7144-7148	JJ	denotes	same
T22148	7154-7155	.	denotes	.
T22149	7155-7282	sentence	denotes	Note that the probe will not detect random integration of the targeting vector because it is external to the targeting vector.
T22150	7156-7160	VB	denotes	Note
T22151	7161-7165	IN	denotes	that
T22152	7185-7191	VB	denotes	detect
T22153	7166-7169	DT	denotes	the
T22154	7170-7175	NN	denotes	probe
T22155	7176-7180	MD	denotes	will
T22156	7181-7184	RB	denotes	not
T22157	7192-7198	JJ	denotes	random
T22158	7199-7210	NN	denotes	integration
T22159	7211-7213	IN	denotes	of
T22160	7214-7217	DT	denotes	the
T22161	7228-7234	NN	denotes	vector
T22162	7218-7227	NN	denotes	targeting
T22163	7235-7242	IN	denotes	because
T22164	7246-7248	VBZ	denotes	is
T22165	7243-7245	PRP	denotes	it
T22166	7249-7257	JJ	denotes	external
T22167	7258-7260	IN	denotes	to
T22168	7261-7264	DT	denotes	the
T22169	7275-7281	NN	denotes	vector
T22170	7265-7274	NN	denotes	targeting
T22171	7281-7282	.	denotes	.
T22172	7282-7517	sentence	denotes	B, Southern blot analysis of Bgll digested genomic DNA derived from the parental wild type ES cell line (R1), a heterozygous targeted ES cell line (362), and from wild type (+/+), heterozygous (+/-) and homozygous knockout (-/-) mice.
T22173	7283-7284	LS	denotes	B
T22174	7300-7308	NN	denotes	analysis
T22175	7284-7286	,	denotes	,
T22176	7286-7294	NNP	denotes	Southern
T22177	7295-7299	NN	denotes	blot
T22178	7309-7311	IN	denotes	of
T22179	7312-7316	NN	denotes	Bgll
T22180	7317-7325	VBN	denotes	digested
T22181	7334-7337	NN	denotes	DNA
T22182	7326-7333	JJ	denotes	genomic
T22183	7338-7345	VBN	denotes	derived
T22184	7346-7350	IN	denotes	from
T22185	7351-7354	DT	denotes	the
T22186	7382-7386	NN	denotes	line
T22187	7355-7363	JJ	denotes	parental
T22188	7364-7368	JJ	denotes	wild
T22189	7369-7373	NN	denotes	type
T22190	7374-7376	NN	denotes	ES
T22191	7377-7381	NN	denotes	cell
T22192	7387-7388	-LRB-	denotes	(
T22193	7388-7390	NN	denotes	R1
T22194	7390-7391	-RRB-	denotes	)
T22195	7391-7393	,	denotes	,
T22196	7393-7394	DT	denotes	a
T22197	7425-7429	NN	denotes	line
T22198	7395-7407	JJ	denotes	heterozygous
T22199	7408-7416	VBN	denotes	targeted
T22200	7417-7419	NN	denotes	ES
T22201	7420-7424	NN	denotes	cell
T22202	7430-7431	-LRB-	denotes	(
T22203	7431-7434	CD	denotes	362
T22204	7434-7435	-RRB-	denotes	)
T22205	7435-7437	,	denotes	,
T22206	7437-7440	CC	denotes	and
T22207	7441-7445	IN	denotes	from
T22208	7446-7450	JJ	denotes	wild
T22209	7451-7455	NN	denotes	type
T22210	7497-7505	NN	denotes	knockout
T22211	7456-7457	-LRB-	denotes	(
T22212	7459-7460	SYM	denotes	+
T22213	7457-7458	SYM	denotes	+
T22214	7458-7459	HYPH	denotes	/
T22215	7460-7461	-RRB-	denotes	)
T22216	7461-7463	,	denotes	,
T22217	7463-7475	JJ	denotes	heterozygous
T22218	7476-7477	-LRB-	denotes	(
T22219	7479-7480	SYM	denotes	-
T22220	7477-7478	SYM	denotes	+
T22221	7478-7479	HYPH	denotes	/
T22222	7480-7481	-RRB-	denotes	)
T22223	7482-7485	CC	denotes	and
T22224	7486-7496	JJ	denotes	homozygous
T22225	7512-7516	NNS	denotes	mice
T22226	7506-7507	-LRB-	denotes	(
T22227	7509-7510	SYM	denotes	-
T22228	7507-7508	SYM	denotes	-
T22229	7508-7509	HYPH	denotes	/
T22230	7510-7511	-RRB-	denotes	)
T22231	7516-7517	.	denotes	.
T22232	7517-7572	sentence	denotes	The blot was hybridized with an Exon 6 specific probe.
T22233	7518-7521	DT	denotes	The
T22234	7522-7526	NN	denotes	blot
T22235	7531-7541	VBN	denotes	hybridized
T22236	7527-7530	VBD	denotes	was
T22237	7542-7546	IN	denotes	with
T22238	7547-7549	DT	denotes	an
T22239	7566-7571	NN	denotes	probe
T22240	7550-7554	NN	denotes	Exon
T22241	7557-7565	JJ	denotes	specific
T22242	7555-7556	CD	denotes	6
T22243	7571-7572	.	denotes	.
T22244	7572-7704	sentence	denotes	C, Immunohistochemical analysis of fresh frozen liver sections from control (+/+) and E2 knockout (-/-) postnatal day 1 mouse pups.
T22245	7573-7574	LS	denotes	C
T22246	7596-7604	NN	denotes	analysis
T22247	7574-7576	,	denotes	,
T22248	7576-7595	JJ	denotes	Immunohistochemical
T22249	7605-7607	IN	denotes	of
T22250	7608-7613	JJ	denotes	fresh
T22251	7614-7620	VBN	denotes	frozen
T22252	7627-7635	NNS	denotes	sections
T22253	7621-7626	NN	denotes	liver
T22254	7636-7640	IN	denotes	from
T22255	7641-7648	NN	denotes	control
T22256	7662-7670	NN	denotes	knockout
T22257	7649-7650	-LRB-	denotes	(
T22258	7652-7653	SYM	denotes	+
T22259	7650-7651	SYM	denotes	+
T22260	7651-7652	HYPH	denotes	/
T22261	7653-7654	-RRB-	denotes	)
T22262	7655-7658	CC	denotes	and
T22263	7659-7661	NN	denotes	E2
T22264	7699-7703	NNS	denotes	pups
T22265	7671-7672	-LRB-	denotes	(
T22266	7674-7675	SYM	denotes	-
T22267	7672-7673	SYM	denotes	-
T22268	7673-7674	HYPH	denotes	/
T22269	7675-7676	-RRB-	denotes	)
T22270	7677-7686	JJ	denotes	postnatal
T22271	7687-7690	NN	denotes	day
T22272	7691-7692	CD	denotes	1
T22273	7693-7698	NN	denotes	mouse
T22274	7703-7704	.	denotes	.
T22275	7704-7799	sentence	denotes	Sections were stained for E2 using an E2 specific antibody (green) and a nuclear stain (blue).
T22276	7705-7713	NNS	denotes	Sections
T22277	7719-7726	VBN	denotes	stained
T22278	7714-7718	VBD	denotes	were
T22279	7727-7730	IN	denotes	for
T22280	7731-7733	NN	denotes	E2
T22281	7734-7739	VBG	denotes	using
T22282	7740-7742	DT	denotes	an
T22283	7755-7763	NN	denotes	antibody
T22284	7743-7745	NN	denotes	E2
T22285	7746-7754	JJ	denotes	specific
T22286	7764-7765	-LRB-	denotes	(
T22287	7765-7770	JJ	denotes	green
T22288	7770-7771	-RRB-	denotes	)
T22289	7772-7775	CC	denotes	and
T22290	7776-7777	DT	denotes	a
T22291	7786-7791	NN	denotes	stain
T22292	7778-7785	JJ	denotes	nuclear
T22293	7792-7793	-LRB-	denotes	(
T22294	7793-7797	JJ	denotes	blue
T22295	7797-7798	-RRB-	denotes	)
T22296	7798-7799	.	denotes	.
T22297	7799-7888	sentence	denotes	Note the complete absence of E2 immunoreactivity in the section from the knockout mouse.
T22298	7800-7804	VB	denotes	Note
T22299	7805-7808	DT	denotes	the
T22300	7818-7825	NN	denotes	absence
T22301	7809-7817	JJ	denotes	complete
T22302	7826-7828	IN	denotes	of
T22303	7829-7831	NN	denotes	E2
T22304	7832-7848	NN	denotes	immunoreactivity
T22305	7849-7851	IN	denotes	in
T22306	7852-7855	DT	denotes	the
T22307	7856-7863	NN	denotes	section
T22308	7864-7868	IN	denotes	from
T22309	7869-7872	DT	denotes	the
T22310	7882-7887	NN	denotes	mouse
T22311	7873-7881	NN	denotes	knockout
T22312	7887-7888	.	denotes	.
T22313	7888-8002	sentence	denotes	D, Similar results were observed upon immunohistochemical analysis of primary mouse embryonic fibroblasts (MEFs).
T22314	7889-7890	LS	denotes	D
T22315	7913-7921	VBN	denotes	observed
T22316	7890-7892	,	denotes	,
T22317	7892-7899	JJ	denotes	Similar
T22318	7900-7907	NNS	denotes	results
T22319	7908-7912	VBD	denotes	were
T22320	7922-7926	IN	denotes	upon
T22321	7927-7946	JJ	denotes	immunohistochemical
T22322	7947-7955	NN	denotes	analysis
T22323	7956-7958	IN	denotes	of
T22324	7959-7966	JJ	denotes	primary
T22325	7983-7994	NNS	denotes	fibroblasts
T22326	7967-7972	NN	denotes	mouse
T22327	7973-7982	JJ	denotes	embryonic
T22328	7995-7996	-LRB-	denotes	(
T22329	7996-8000	NNS	denotes	MEFs
T22330	8000-8001	-RRB-	denotes	)
T22331	8001-8002	.	denotes	.
T22332	8002-8162	sentence	denotes	Note that the readily detectable signal for E2 in the control cells was present in a pattern characteristic of mitochondria, the subcellular location of BCKDH.
T22333	8003-8007	VB	denotes	Note
T22334	8008-8012	IN	denotes	that
T22335	8071-8074	VBD	denotes	was
T22336	8013-8016	DT	denotes	the
T22337	8036-8042	NN	denotes	signal
T22338	8017-8024	RB	denotes	readily
T22339	8025-8035	JJ	denotes	detectable
T22340	8043-8046	IN	denotes	for
T22341	8047-8049	NN	denotes	E2
T22342	8050-8052	IN	denotes	in
T22343	8053-8056	DT	denotes	the
T22344	8065-8070	NNS	denotes	cells
T22345	8057-8064	NN	denotes	control
T22346	8075-8082	JJ	denotes	present
T22347	8083-8085	IN	denotes	in
T22348	8086-8087	DT	denotes	a
T22349	8088-8095	NN	denotes	pattern
T22350	8096-8110	JJ	denotes	characteristic
T22351	8111-8113	IN	denotes	of
T22352	8114-8126	NNS	denotes	mitochondria
T22353	8126-8128	,	denotes	,
T22354	8128-8131	DT	denotes	the
T22355	8144-8152	NN	denotes	location
T22356	8132-8143	JJ	denotes	subcellular
T22357	8153-8155	IN	denotes	of
T22358	8156-8161	NN	denotes	BCKDH
T22359	8161-8162	.	denotes	.
T22807	17357-17368	JJ	denotes	Biochemical
T22808	17369-17385	NN	denotes	characterization
T22809	17386-17388	IN	denotes	of
T22810	17389-17392	DT	denotes	the
T22811	17413-17418	NN	denotes	model
T22812	17393-17400	JJ	denotes	classic
T22813	17401-17405	NN	denotes	MSUD
T22814	17406-17412	JJ	denotes	murine
T22815	17418-17419	.	denotes	.
T22816	17419-17545	sentence	denotes	A, BCKDH enzyme activity in liver of newborn wild type control (+/+), heterozygous (+/-), and homozygous (-/-) knockout mice.
T22817	17420-17421	LS	denotes	A
T22818	17436-17444	NN	denotes	activity
T22819	17421-17423	,	denotes	,
T22820	17423-17428	NN	denotes	BCKDH
T22821	17429-17435	NN	denotes	enzyme
T22822	17445-17447	IN	denotes	in
T22823	17448-17453	NN	denotes	liver
T22824	17454-17456	IN	denotes	of
T22825	17457-17464	JJ	denotes	newborn
T22826	17540-17544	NNS	denotes	mice
T22827	17465-17469	JJ	denotes	wild
T22828	17470-17474	NN	denotes	type
T22829	17475-17482	NN	denotes	control
T22830	17531-17539	NN	denotes	knockout
T22831	17483-17484	-LRB-	denotes	(
T22832	17486-17487	SYM	denotes	+
T22833	17484-17485	SYM	denotes	+
T22834	17485-17486	HYPH	denotes	/
T22835	17487-17488	-RRB-	denotes	)
T22836	17488-17490	,	denotes	,
T22837	17490-17502	JJ	denotes	heterozygous
T22838	17503-17504	-LRB-	denotes	(
T22839	17506-17507	SYM	denotes	-
T22840	17504-17505	SYM	denotes	+
T22841	17505-17506	HYPH	denotes	/
T22842	17507-17508	-RRB-	denotes	)
T22843	17508-17510	,	denotes	,
T22844	17510-17513	CC	denotes	and
T22845	17514-17524	JJ	denotes	homozygous
T22846	17525-17526	-LRB-	denotes	(
T22847	17528-17529	SYM	denotes	-
T22848	17526-17527	SYM	denotes	-
T22849	17527-17528	HYPH	denotes	/
T22850	17529-17530	-RRB-	denotes	)
T22851	17544-17545	.	denotes	.
T22852	17545-17668	sentence	denotes	Enzyme activity was significantly reduced in +/- liver compared to +/+, and was below the level of detection in -/- liver.
T22853	17546-17552	NN	denotes	Enzyme
T22854	17553-17561	NN	denotes	activity
T22855	17562-17565	VBD	denotes	was
T22856	17566-17579	RB	denotes	significantly
T22857	17580-17587	JJ	denotes	reduced
T22858	17588-17590	IN	denotes	in
T22859	17591-17592	SYM	denotes	+
T22860	17593-17594	SYM	denotes	-
T22861	17592-17593	HYPH	denotes	/
T22862	17595-17600	NN	denotes	liver
T22863	17601-17609	VBN	denotes	compared
T22864	17610-17612	IN	denotes	to
T22865	17613-17614	SYM	denotes	+
T22866	17615-17616	SYM	denotes	+
T22867	17614-17615	HYPH	denotes	/
T22868	17616-17618	,	denotes	,
T22869	17618-17621	CC	denotes	and
T22870	17622-17625	VBD	denotes	was
T22871	17626-17631	IN	denotes	below
T22872	17632-17635	DT	denotes	the
T22873	17636-17641	NN	denotes	level
T22874	17642-17644	IN	denotes	of
T22875	17645-17654	NN	denotes	detection
T22876	17655-17657	IN	denotes	in
T22877	17658-17659	SYM	denotes	-
T22878	17660-17661	SYM	denotes	-
T22879	17659-17660	HYPH	denotes	/
T22880	17662-17667	NN	denotes	liver
T22881	17667-17668	.	denotes	.
T22882	17668-17715	sentence	denotes	B, Total BCAA concentrations in blood of mice.
T22883	17669-17670	LS	denotes	B
T22884	17683-17697	NNS	denotes	concentrations
T22885	17670-17672	,	denotes	,
T22886	17672-17677	JJ	denotes	Total
T22887	17678-17682	NN	denotes	BCAA
T22888	17698-17700	IN	denotes	in
T22889	17701-17706	NN	denotes	blood
T22890	17707-17709	IN	denotes	of
T22891	17710-17714	NNS	denotes	mice
T22892	17714-17715	.	denotes	.
T22893	17715-17780	sentence	denotes	Total BCAA represent the sum of leucine, isoleucine, and valine.
T22894	17716-17721	JJ	denotes	Total
T22895	17722-17726	NN	denotes	BCAA
T22896	17727-17736	VBP	denotes	represent
T22897	17737-17740	DT	denotes	the
T22898	17741-17744	NN	denotes	sum
T22899	17745-17747	IN	denotes	of
T22900	17748-17755	NN	denotes	leucine
T22901	17755-17757	,	denotes	,
T22902	17757-17767	NN	denotes	isoleucine
T22903	17767-17769	,	denotes	,
T22904	17769-17772	CC	denotes	and
T22905	17773-17779	NN	denotes	valine
T22906	17779-17780	.	denotes	.
T22907	17780-17882	sentence	denotes	Total BCAA concentrations in blood from -/- mice were significantly elevated compared to +/+ and +/-.
T22908	17781-17786	JJ	denotes	Total
T22909	17792-17806	NNS	denotes	concentrations
T22910	17787-17791	NN	denotes	BCAA
T22911	17830-17834	VBD	denotes	were
T22912	17807-17809	IN	denotes	in
T22913	17810-17815	NN	denotes	blood
T22914	17816-17820	IN	denotes	from
T22915	17821-17822	SYM	denotes	-
T22916	17823-17824	SYM	denotes	-
T22917	17822-17823	HYPH	denotes	/
T22918	17825-17829	NNS	denotes	mice
T22919	17835-17848	RB	denotes	significantly
T22920	17849-17857	JJ	denotes	elevated
T22921	17858-17866	VBN	denotes	compared
T22922	17867-17869	IN	denotes	to
T22923	17870-17871	SYM	denotes	+
T22924	17872-17873	SYM	denotes	+
T22925	17871-17872	HYPH	denotes	/
T22926	17874-17877	CC	denotes	and
T22927	17878-17879	SYM	denotes	+
T22928	17880-17881	SYM	denotes	-
T22929	17879-17880	HYPH	denotes	/
T22930	17881-17882	.	denotes	.
T22931	17882-17934	sentence	denotes	C, Ratio of total BCAA to alanine in blood of mice.
T22932	17883-17884	LS	denotes	C
T22933	17886-17891	NN	denotes	Ratio
T22934	17884-17886	,	denotes	,
T22935	17892-17894	IN	denotes	of
T22936	17895-17900	JJ	denotes	total
T22937	17901-17905	NN	denotes	BCAA
T22938	17906-17908	IN	denotes	to
T22939	17909-17916	NN	denotes	alanine
T22940	17917-17919	IN	denotes	in
T22941	17920-17925	NN	denotes	blood
T22942	17926-17928	IN	denotes	of
T22943	17929-17933	NNS	denotes	mice
T22944	17933-17934	.	denotes	.
T22945	17934-18014	sentence	denotes	This ratio was significantly elevated in -/- mice compared to +/+ and +/- mice.
T22946	17935-17939	DT	denotes	This
T22947	17940-17945	NN	denotes	ratio
T22948	17946-17949	VBD	denotes	was
T22949	17950-17963	RB	denotes	significantly
T22950	17964-17972	JJ	denotes	elevated
T22951	17973-17975	IN	denotes	in
T22952	17976-17977	SYM	denotes	-
T22953	17978-17979	SYM	denotes	-
T22954	17977-17978	HYPH	denotes	/
T22955	17980-17984	NNS	denotes	mice
T22956	17985-17993	VBN	denotes	compared
T22957	17994-17996	IN	denotes	to
T22958	17997-17998	SYM	denotes	+
T22959	17999-18000	SYM	denotes	+
T22960	17998-17999	HYPH	denotes	/
T22961	18009-18013	NNS	denotes	mice
T22962	18001-18004	CC	denotes	and
T22963	18005-18006	SYM	denotes	+
T22964	18007-18008	SYM	denotes	-
T22965	18006-18007	HYPH	denotes	/
T22966	18013-18014	.	denotes	.
T22967	18014-18077	sentence	denotes	The numbers on the bars indicates the number of mice analyzed.
T22968	18015-18018	DT	denotes	The
T22969	18019-18026	NNS	denotes	numbers
T22970	18039-18048	VBZ	denotes	indicates
T22971	18027-18029	IN	denotes	on
T22972	18030-18033	DT	denotes	the
T22973	18034-18038	NNS	denotes	bars
T22974	18049-18052	DT	denotes	the
T22975	18053-18059	NN	denotes	number
T22976	18060-18062	IN	denotes	of
T22977	18063-18067	NNS	denotes	mice
T22978	18068-18076	VBN	denotes	analyzed
T22979	18076-18077	.	denotes	.
T22980	18077-18184	sentence	denotes	, Significantly different from +/+ (P < 0.001); *, significantly different from +/+ and +/- (P < 0.001).
T22981	18078-18079	SYM	denotes	*
T22982	18127-18129	SYM	denotes	**
T22983	18079-18081	,	denotes	,
T22984	18081-18094	RB	denotes	Significantly
T22985	18095-18104	JJ	denotes	different
T22986	18105-18109	IN	denotes	from
T22987	18110-18111	SYM	denotes	+
T22988	18112-18113	SYM	denotes	+
T22989	18111-18112	HYPH	denotes	/
T22990	18114-18115	-LRB-	denotes	(
T22991	18119-18124	CD	denotes	0.001
T22992	18115-18116	NN	denotes	P
T22993	18117-18118	SYM	denotes	<
T22994	18124-18125	-RRB-	denotes	)
T22995	18125-18126	:	denotes	;
T22996	18129-18131	,	denotes	,
T22997	18131-18144	RB	denotes	significantly
T22998	18145-18154	JJ	denotes	different
T22999	18155-18159	IN	denotes	from
T23000	18160-18161	SYM	denotes	+
T23001	18162-18163	SYM	denotes	+
T23002	18161-18162	HYPH	denotes	/
T23003	18164-18167	CC	denotes	and
T23004	18168-18169	SYM	denotes	+
T23005	18170-18171	SYM	denotes	-
T23006	18169-18170	HYPH	denotes	/
T23007	18172-18173	-LRB-	denotes	(
T23008	18177-18182	CD	denotes	0.001
T23009	18173-18174	NN	denotes	P
T23010	18175-18176	SYM	denotes	<
T23011	18182-18183	-RRB-	denotes	)
T23012	18183-18184	.	denotes	.
T23928	23018-23019	.	denotes	.
T24488	25414-25416	IN	denotes	of
T24487	25405-25413	NN	denotes	knockout
T24486	25401-25404	IN	denotes	for
T24485	25388-25390	,	denotes	,
T24484	25384-25388	FW	denotes	i.e.
T24483	25390-25400	JJ	denotes	homozygous
T24687	26316-26321	NNS	denotes	cages
T24686	26310-26315	PRP$	denotes	their
T24685	26307-26309	IN	denotes	in
T24684	26302-26306	JJ	denotes	dead
T24683	26296-26301	VBN	denotes	found
T24682	26291-26295	VBD	denotes	were
T24681	26288-26290	CC	denotes	or
T24774	19978-19985	NN	denotes	Summary
T24775	19986-19988	IN	denotes	of
T24776	19989-19999	JJ	denotes	additional
T24777	20017-20023	NNS	denotes	levels
T24778	20000-20005	NN	denotes	blood
T24779	20006-20011	NN	denotes	amino
T24780	20012-20016	NN	denotes	acid
T24781	20024-20026	IN	denotes	in
T24782	20027-20030	DT	denotes	the
T24783	20044-20049	NN	denotes	model
T24784	20031-20038	JJ	denotes	classic
T24785	20039-20043	NN	denotes	MSUD
T24786	20050-20053	CC	denotes	and
T24787	20054-20061	NN	denotes	control
T24788	20062-20073	NNS	denotes	littermates
T24789	20074-20076	IN	denotes	as
T24790	20077-20087	VBN	denotes	determined
T24791	20088-20090	IN	denotes	by
T24792	20091-20097	JJ	denotes	tandem
T24793	20103-20115	NN	denotes	spectrometry
T24794	20098-20102	NN	denotes	mass
T24795	20115-20116	.	denotes	.
T24796	20116-20164	sentence	denotes	All samples were collected on the day of birth.
T24797	20117-20120	DT	denotes	All
T24798	20121-20128	NNS	denotes	samples
T24799	20134-20143	VBN	denotes	collected
T24800	20129-20133	VBD	denotes	were
T24801	20144-20146	IN	denotes	on
T24802	20147-20150	DT	denotes	the
T24803	20151-20154	NN	denotes	day
T24804	20155-20157	IN	denotes	of
T24805	20158-20163	NN	denotes	birth
T24806	20163-20164	.	denotes	.
T24807	20164-20193	sentence	denotes	All values are mean +/- SEM.
T24808	20165-20168	DT	denotes	All
T24809	20169-20175	NNS	denotes	values
T24810	20176-20179	VBP	denotes	are
T24811	20180-20184	NN	denotes	mean
T24812	20185-20186	SYM	denotes	+
T24813	20186-20187	HYPH	denotes	/
T24814	20187-20188	SYM	denotes	-
T24815	20189-20192	NN	denotes	SEM
T24816	20192-20193	.	denotes	.
T12690	19814-19818	IN	denotes	than
T12691	19821-19825	RB	denotes	fold
T12692	19820-19821	HYPH	denotes	-
T12693	19826-19832	JJR	denotes	higher
T12694	19833-19837	IN	denotes	than
T12695	19838-19839	SYM	denotes	+
T12696	19840-19841	SYM	denotes	+
T12697	19839-19840	HYPH	denotes	/
T12240	16941-16946	NN	denotes	mouse
T12241	16952-16959	VBN	denotes	derived
T12242	16960-16964	IN	denotes	from
T12243	16965-16966	SYM	denotes	+
T12244	16967-16968	SYM	denotes	-
T12245	16966-16967	HYPH	denotes	/
T12246	16983-16988	NNS	denotes	pairs
T12338	18185-18278	sentence	denotes	Immunohistochemistry with an E2 specific antibody was used to examine E2 protein in the mice.
T12339	18185-18205	NN	denotes	Immunohistochemistry
T12340	18239-18243	VBN	denotes	used
T12341	18206-18210	IN	denotes	with
T12342	18211-18213	DT	denotes	an
T12343	18226-18234	NN	denotes	antibody
T12344	18214-18216	NN	denotes	E2
T12345	18217-18225	JJ	denotes	specific
T12698	19849-19860	NNS	denotes	littermates
T12663	19713-19716	DT	denotes	the
T12664	19728-19735	NNS	denotes	results
T12665	19717-19722	NN	denotes	amino
T12666	19723-19727	NN	denotes	acid
T12667	19736-19738	IN	denotes	as
T12668	19739-19743	NN	denotes	BCAA
T12669	19744-19751	NN	denotes	alanine
T12670	19743-19744	HYPH	denotes	/
T12671	19752-19757	NN	denotes	ratio
T12672	19757-19758	.	denotes	.
T12673	19758-19861	sentence	denotes	As shown in Figure 2C, this ratio in -/- pups was more than 6-fold higher than +/+ or +/- littermates.
T12674	19759-19761	IN	denotes	As
T12675	19762-19767	VBN	denotes	shown
T12676	19805-19808	VBD	denotes	was
T12677	19768-19770	IN	denotes	in
T12678	19771-19777	NN	denotes	Figure
T12679	19778-19780	NN	denotes	2C
T12680	19780-19782	,	denotes	,
T12681	19782-19786	DT	denotes	this
T12682	19787-19792	NN	denotes	ratio
T12683	19793-19795	IN	denotes	in
T12684	19796-19797	SYM	denotes	-
T12685	19798-19799	SYM	denotes	-
T12686	19797-19798	HYPH	denotes	/
T12687	19800-19804	NNS	denotes	pups
T12688	19809-19813	RBR	denotes	more
T12689	19819-19820	CD	denotes	6
T12699	19842-19844	CC	denotes	or
T12700	19845-19846	SYM	denotes	+
T12737	20527-20535	NN	denotes	activity
T12736	20511-20516	NN	denotes	BCKDH
T12735	20492-20500	NN	denotes	knockout
T12734	20501-20505	NNS	denotes	mice
T12733	20489-20491	NN	denotes	E2
T12732	20487-20489	,	denotes	,
T12731	20480-20487	NN	denotes	summary
T12730	20506-20510	VBP	denotes	lack
T12729	20477-20479	IN	denotes	In
T12728	19968-20623	sentence	denotes	Table 1 Summary of additional blood amino acid levels in the classic MSUD model and control littermates as determined by tandem mass spectrometry. All samples were collected on the day of birth. All values are mean +/- SEM. MSUD Genotype Alanine Glutamate Glutamine (μmole/L) +/+ 196.1 ± 23.1 (6) 229.0 ± 12.0 (6) 76.8 ± 3.0 (6) +/- 167.6 ± 9.9 (13) 251.0 ± 12.8 (13) 72.3 ± 1.6 (13) -/- 94.6 ± 11.6* (5) 107.8 ± 4.8* (5) 50.4 ± 2.9* (5) *: Significantly different from +/+ and +/- (P < 0.001). In summary, E2 knockout mice lack BCKDH enzymatic activity, E2 immunoreactivity, and have markedly elevated levels of BCAA in the blood and urine.
T3304	11-16	NN	denotes	Maple
T3305	17-22	NN	denotes	Syrup
T3306	29-36	NN	denotes	Disease
T3307	23-28	NN	denotes	Urine
T3308	44-46	VBZ	denotes	is
T3309	37-38	-LRB-	denotes	(
T3310	38-42	NN	denotes	MSUD
T3311	42-43	-RRB-	denotes	)
T3312	47-48	DT	denotes	a
T3313	57-65	NN	denotes	disorder
T3314	49-56	JJ	denotes	genetic
T3315	66-72	VBN	denotes	caused
T3316	73-75	IN	denotes	by
T3317	76-77	DT	denotes	a
T15938	23079-23082	DT	denotes	the
T15937	23076-23078	IN	denotes	by
T15936	23072-23075	VBN	denotes	zed
T15935	23071-23072	NNS	denotes	i
T15934	23071-23106	sentence	denotes	ized by the Bujard laboratory [34].
T15900	23028-23032	NNS	denotes	mice
T15899	23023-23024	HYPH	denotes	-
T15898	23024-23027	NN	denotes	tTA
T15897	23020-23023	NN	denotes	LAP
T15896	23020-23033	sentence	denotes	LAP-tTA mice
T15895	21733-21734	sentence	denotes
T15894	21732-21733	.	denotes	.
T15893	21729-21732	NN	denotes	tTA
T15892	21726-21728	IN	denotes	by
T15891	21714-21725	NN	denotes	stimulation
T15890	21709-21713	IN	denotes	upon
T15889	21700-21708	NN	denotes	promoter
T15911	23044-23045	NN	denotes	u
T15910	23043-23044	VB	denotes	o
T15909	23043-23049	sentence	denotes	ously
T15908	23042-23043	JJ	denotes	i
T15907	23041-23042	NN	denotes	v
T15906	23038-23041	NN	denotes	pre
T15905	23038-23043	sentence	denotes	previ
T15904	23035-23037	VB	denotes	re
T15903	23033-23034	VBD	denotes	w
T15902	23034-23035	VBN	denotes	e
T15901	23033-23038	sentence	denotes	were
T15917	23052-23053	NN	denotes	d
T15916	23049-23052	NN	denotes	pro
T15915	23049-23056	sentence	denotes	produce
T15914	23047-23048	JJ	denotes	y
T15913	23046-23047	JJ	denotes	l
T15912	23045-23046	NNS	denotes	s
T15959	23191-23193	NN	denotes	E2
T15958	23187-23190	NN	denotes	TRE
T15957	23194-23203	NN	denotes	transgene
T15956	23183-23186	DT	denotes	the
T15955	23174-23182	VBD	denotes	harbored
T15954	23169-23173	WDT	denotes	that
T15953	23164-23168	NNS	denotes	mice
T15952	23153-23163	JJ	denotes	transgenic
T15951	23145-23152	VB	denotes	produce
T15950	23142-23144	TO	denotes	to
T15949	23133-23136	VBD	denotes	was
T15948	23137-23141	VBN	denotes	used
T15947	23118-23132	NN	denotes	microinjection
T15946	23107-23117	JJ	denotes	Pronuclear
T15945	23106-23204	sentence	denotes	Pronuclear microinjection was used to produce transgenic mice that harbored the TRE-E2 transgene.
T15944	23105-23106	.	denotes	.
T15943	23104-23105	-RRB-	denotes	]
T15942	23102-23104	CD	denotes	34
T15941	23101-23102	-LRB-	denotes	[
T15940	23083-23089	NNP	denotes	Bujard
T15939	23090-23100	NN	denotes	laboratory
T15933	23069-23070	VB	denotes	e
T15932	23068-23069	TO	denotes	t
T15931	23067-23068	DT	denotes	c
T15930	23066-23067	VBN	denotes	a
T15929	23065-23066	NN	denotes	r
T15928	23070-23071	VBN	denotes	r
T15927	23064-23065	DT	denotes	a
T15926	23064-23071	sentence	denotes	aracter
T15925	23063-23064	DT	denotes	h
T15924	23062-23063	NN	denotes	c
T15923	23058-23061	CC	denotes	and
T15922	23056-23057	NN	denotes	d
T15921	23056-23064	sentence	denotes	d and ch
T15920	23055-23056	NNS	denotes	e
T15919	23054-23055	JJ	denotes	c
T15918	23053-23054	JJ	denotes	u
T16321	25082-25091	VBG	denotes	surviving
T16320	25066-25072	VBN	denotes	tested
T16319	25073-25081	VBD	denotes	produced
T16318	25054-25059	JJ	denotes	other
T16317	25060-25065	NNS	denotes	lines
T16316	25050-25053	DT	denotes	All
T16315	25049-25154	sentence	denotes	All other lines tested produced surviving rescue animals at a frequency between 1 and 5% of weaned pups.
T16314	25048-25049	.	denotes	.
T16285	24883-24885	TO	denotes	to
T16284	24860-24864	NN	denotes	525A
T16283	24865-24874	NN	denotes	transgene
T16282	24856-24859	DT	denotes	the
T16281	24854-24856	,	denotes	,
T16280	24875-24882	VBZ	denotes	appears
T16279	24850-24854	RB	denotes	Thus
T16278	24849-24967	sentence	denotes	Thus, the 525A transgene appears to be highly effective at rescuing the neonatal lethal phenotype of the E2 knockout.
T16313	25032-25038	JJ	denotes	lethal
T16312	25023-25031	JJ	denotes	neonatal
T16311	25039-25048	NN	denotes	phenotype
T16310	25019-25022	DT	denotes	the
T16309	25012-25018	VB	denotes	rescue
T16308	25009-25011	TO	denotes	to
T16307	24991-25001	RB	denotes	completely
T16306	24986-24990	NN	denotes	520B
T16305	24981-24985	NN	denotes	line
T16304	24979-24981	,	denotes	,
T16303	24971-24979	NN	denotes	contrast
T16302	25002-25008	VBD	denotes	failed
T16301	24968-24970	IN	denotes	In
T16300	24967-25049	sentence	denotes	In contrast, line 520B completely failed to rescue the neonatal lethal phenotype.
T16299	24966-24967	.	denotes	.
T16298	24955-24957	NN	denotes	E2
T16297	24958-24966	NN	denotes	knockout
T16296	24951-24954	DT	denotes	the
T16295	24948-24950	IN	denotes	of
T16294	24931-24937	JJ	denotes	lethal
T16293	24922-24930	JJ	denotes	neonatal
T16292	24938-24947	NN	denotes	phenotype
T16291	24918-24921	DT	denotes	the
T16290	24909-24917	VBG	denotes	rescuing
T16289	24906-24908	IN	denotes	at
T16288	24896-24905	JJ	denotes	effective
T16287	24889-24895	RB	denotes	highly
T16286	24886-24888	VB	denotes	be
T16355	26348-26349	NNS	denotes	e
T16354	26347-26348	NNS	denotes	l
T16353	26346-26347	JJR	denotes	e
T16352	26345-26346	RB	denotes	s
T16351	26340-26344	VBD	denotes	were
T16350	26340-26349	sentence	denotes	were sele
T16349	26339-26340	sentence	denotes
T16348	26335-26339	NN	denotes	525A
T16347	26333-26334	NN	denotes	d
T16346	26331-26333	NN	denotes	an
T16345	26329-26330	NN	denotes	A
T16344	26329-26339	sentence	denotes	A and 525A
T16343	26327-26328	VBZ	denotes	s
T16342	26326-26327	NN	denotes	e
T16341	26325-26326	NN	denotes	n
T16340	26324-26325	VBZ	denotes	i
T16339	26324-26329	sentence	denotes	ines
T16338	26323-26324	NN	denotes	L
T16379	26384-26486	sentence	denotes	Fig. 4B shows the results of blood amino acid analysis presented as a ratio of total BCAA to alanine.
T16378	26383-26384	.	denotes	.
T16377	26372-26383	NN	denotes	cterization
T16376	26371-26372	VBN	denotes	a
T16375	26370-26371	VBD	denotes	r
T16374	26370-26384	sentence	denotes	racterization.
T16373	26369-26370	NNS	denotes	a
T16372	26368-26369	PRP$	denotes	h
T16371	26367-26368	VBN	denotes	c
T16370	26365-26366	JJ	denotes	d
T16369	26364-26365	PRP	denotes	e
T16368	26363-26364	IN	denotes	l
T16367	26361-26363	NN	denotes	ai
T16366	26360-26361	IN	denotes	t
T16365	26360-26370	sentence	denotes	tailed cha
T16364	26359-26360	NNS	denotes	e
T16363	26358-26359	CC	denotes	d
T16362	26355-26357	NN	denotes	or
T16361	26354-26355	IN	denotes	f
T16360	26354-26360	sentence	denotes	for de
T16359	26353-26354	sentence	denotes
T16358	26352-26353	VBN	denotes	d
T16357	26349-26352	VBZ	denotes	cte
T16356	26349-26353	sentence	denotes	cted
T16382	26393-26398	VBZ	denotes	shows
T16381	26390-26392	NN	denotes	4B
T16380	26385-26389	NN	denotes	Fig.
T16501	27621-27625	VBP	denotes	have
T16500	27612-27617	JJ	denotes	human
T16499	27618-27620	NN	denotes	E2
T16498	27601-27611	JJ	denotes	transgenic
T16497	27598-27600	IN	denotes	of
T16496	27587-27597	NN	denotes	expression
T16495	27581-27586	VB	denotes	drive
T16494	27578-27580	TO	denotes	to
T16493	27568-27572	VBD	denotes	were
T16492	27573-27577	VBN	denotes	used
T16491	27563-27567	WDT	denotes	that
T16490	27553-27554	HYPH	denotes	-
T16489	27554-27557	NN	denotes	tTA
T16488	27550-27553	NN	denotes	LAP
T16487	27558-27562	NNS	denotes	mice
T16486	27546-27549	DT	denotes	the
T16485	27631-27643	VBN	denotes	demonstrated
T16484	27538-27545	IN	denotes	Because
T16483	27538-27786	sentence	denotes	Because the LAP-tTA mice that were used to drive expression of transgenic human E2 have been demonstrated to produce liver specific expression [34], BCKDH enzyme activity and production of human E2 protein in liver of Lines A and 525A was examined.
R348	T3304	T3305	compound	Maple,Syrup
R349	T3305	T3306	compound	Syrup,Disease
R350	T3306	T3308	nsubj	Disease,is
R351	T3307	T3306	compound	Urine,Disease
R352	T3309	T3306	punct	(,Disease
R353	T3310	T3306	appos	MSUD,Disease
R354	T3311	T3308	punct	),is
R355	T3312	T3313	det	a,disorder
R356	T3313	T3308	attr	disorder,is
R357	T3314	T3313	amod	genetic,disorder
R358	T3315	T3313	acl	caused,disorder
R359	T3316	T3315	agent	by,caused
R360	T3317	T3318	det	a,deficiency
R361	T3318	T3316	pobj	deficiency,by
R362	T3319	T3318	prep	of,deficiency
R363	T3320	T3321	amod	branched,chain
R364	T3321	T3323	compound	chain,dehydrogenase
R365	T3322	T3321	punct	-,chain
R366	T3323	T3319	pobj	dehydrogenase,of
R367	T3324	T3325	compound	keto,acid
R368	T3325	T3323	compound	acid,dehydrogenase
R369	T3326	T3323	punct	(,dehydrogenase
R370	T3327	T3323	appos	BCKDH,dehydrogenase
R371	T3328	T3318	punct	),deficiency
R372	T3329	T3318	punct	", ",deficiency
R373	T3330	T3331	det	a,complex
R374	T3331	T3318	appos	complex,deficiency
R375	T3332	T3331	amod	mitochondrial,complex
R376	T3333	T3331	compound	multienzyme,complex
R377	T3334	T3331	amod	responsible,complex
R378	T3335	T3334	prep	for,responsible
R379	T3336	T3337	det	the,decarboxylation
R380	T3337	T3335	pobj	decarboxylation,for
R381	T3338	T3337	amod	oxidative,decarboxylation
R382	T3339	T3337	prep	of,decarboxylation
R383	T3423	T3422	prep	of,%
R384	T3340	T3341	amod	branched,chain
R385	T3424	T3423	pobj	normal,of
R386	T3425	T3426	punct	[,1
R387	T3341	T3343	compound	chain,acids
R388	T3426	T3402	parataxis	1,have
R389	T3427	T3426	punct	],1
R390	T3428	T3402	punct	.,have
R391	T3430	T3431	det	These,patients
R392	T3431	T3432	nsubj	patients,show
R393	T3433	T3434	advmod	markedly,elevated
R394	T3434	T3435	amod	elevated,levels
R395	T3435	T3432	dobj	levels,show
R396	T3342	T3341	punct	-,chain
R397	T3436	T3435	prep	of,levels
R398	T3437	T3436	pobj	BCAA,of
R399	T3438	T3432	prep	in,show
R400	T3439	T3438	pobj	blood,in
R401	T3343	T3339	pobj	acids,of
R402	T3440	T3439	cc	and,blood
R403	T3441	T3442	amod	other,fluids
R404	T3344	T3343	compound	keto,acids
R405	T3442	T3439	conj	fluids,blood
R406	T3443	T3442	compound	body,fluids
R407	T3444	T3445	punct	[,1
R408	T3345	T3343	acl	derived,acids
R409	T3445	T3432	parataxis	1,show
R410	T3446	T3445	punct	],1
R411	T3447	T3432	punct	.,show
R412	T3346	T3345	prep	from,derived
R413	T3449	T3450	prep	Besides,are
R414	T3347	T3348	amod	branched,chain
R415	T3451	T3452	det	the,form
R416	T3452	T3449	pobj	form,Besides
R417	T3348	T3350	compound	chain,acids
R418	T3453	T3452	amod	classic,form
R419	T3454	T3450	punct	", ",are
R420	T3455	T3450	expl	there,are
R421	T3349	T3348	punct	-,chain
R422	T3456	T3457	amod	other,variants
R423	T3350	T3346	pobj	acids,from
R424	T3457	T3450	attr	variants,are
R425	T3458	T3457	prep	of,variants
R426	T3459	T3460	det	the,disease
R427	T3460	T3458	pobj	disease,of
R428	T3351	T3350	compound	amino,acids
R429	T3461	T3450	punct	.,are
R430	T3463	T3464	nsubj	Patients,show
R431	T3352	T3350	punct	(,acids
R432	T3465	T3463	prep	with,Patients
R433	T3466	T3467	det	the,form
R434	T3353	T3350	appos	BCAA,acids
R435	T3354	T3350	punct	),acids
R436	T3467	T3465	pobj	form,with
R437	T3468	T3467	amod	intermediate,form
R438	T3355	T3350	punct	", ",acids
R439	T3469	T3467	prep	of,form
R440	T3470	T3471	det	the,disease
R441	T3471	T3469	pobj	disease,of
R442	T3472	T3473	compound	BCKDH,activity
R443	T3473	T3464	dobj	activity,show
R444	T3474	T3473	prep	in,activity
R445	T3356	T3350	conj	leucine,acids
R446	T3475	T3476	det	the,range
R447	T3476	T3474	pobj	range,in
R448	T3477	T3476	prep	of,range
R449	T3357	T3356	punct	", ",leucine
R450	T3478	T3479	quantmod	3,30
R451	T3479	T3481	nummod	30,%
R452	T3480	T3479	punct	–,30
R453	T3358	T3356	conj	isoleucine,leucine
R454	T3481	T3477	pobj	%,of
R455	T3482	T3481	prep	of,%
R456	T3483	T3482	pobj	normal,of
R457	T3359	T3358	cc	and,isoleucine
R458	T3484	T3464	punct	.,show
R459	T3486	T3487	prep	In,delayed
R460	T3360	T3358	conj	valine,isoleucine
R461	T3488	T3489	amod	such,patients
R462	T3489	T3486	pobj	patients,In
R463	T3361	T3362	punct	(,see
R464	T3490	T3491	det	the,onset
R465	T3491	T3487	nsubjpass	onset,delayed
R466	T3362	T3308	parataxis	see,is
R467	T3492	T3491	prep	of,onset
R468	T3493	T3494	det	the,disease
R469	T3494	T3492	pobj	disease,of
R470	T3495	T3487	auxpass	is,delayed
R471	T3363	T3362	prep	for,see
R472	T3496	T3487	punct	", ",delayed
R473	T3497	T3487	cc	but,delayed
R474	T3498	T3499	expl	there,are
R475	T3364	T3363	pobj	review,for
R476	T3499	T3487	conj	are,delayed
R477	T3365	T3362	punct	", ",see
R478	T3500	T3501	advmod	persistently,elevated
R479	T3501	T3502	amod	elevated,levels
R480	T3502	T3499	attr	levels,are
R481	T3503	T3502	prep	of,levels
R482	T3366	T3362	punct	: ,see
R483	T3504	T3503	pobj	BCAA,of
R484	T3505	T3506	punct	[,1
R485	T3367	T3362	punct	[,see
R486	T3506	T3499	parataxis	1,are
R487	T3507	T3506	punct	],1
R488	T3508	T3499	punct	.,are
R489	T3368	T3362	dobj	1,see
R490	T3510	T3511	nsubj	Patients,show
R491	T3369	T3362	punct	],see
R492	T3512	T3510	prep	with,Patients
R493	T3513	T3514	det	the,form
R494	T3514	T3512	pobj	form,with
R495	T3515	T3514	amod	intermittent,form
R496	T3516	T3514	prep	of,form
R497	T3370	T3362	punct	),see
R498	T3517	T3516	pobj	MSUD,of
R499	T3518	T3519	compound	BCKDH,activity
R500	T3519	T3511	dobj	activity,show
R501	T3520	T3511	prep	in,show
R502	T3371	T3308	punct	.,is
R503	T3521	T3522	det	the,range
R504	T3522	T3520	pobj	range,in
R505	T3523	T3522	prep	of,range
R506	T3373	T3374	nsubj	Patients,show
R507	T3524	T3525	quantmod	5,20
R508	T3525	T3527	nummod	20,%
R509	T3526	T3525	punct	–,20
R510	T3527	T3523	pobj	%,of
R511	T3375	T3373	prep	with,Patients
R512	T3528	T3511	cc	and,show
R513	T3376	T3375	pobj	MSUD,with
R514	T3377	T3374	punct	", ",show
R515	T3378	T3374	prep	depending,show
R516	T3529	T3530	prep	during,are
R517	T3530	T3511	conj	are,show
R518	T3379	T3378	prep	on,depending
R519	T3531	T3532	det	the,phase
R520	T3532	T3529	pobj	phase,during
R521	T3380	T3381	det	the,mutation
R522	T3533	T3532	amod	asymptomatic,phase
R523	T3534	T3535	det	the,levels
R524	T3535	T3530	nsubj	levels,are
R525	T3381	T3379	pobj	mutation,on
R526	T3536	T3535	compound	blood,levels
R527	T3537	T3535	compound	BCAA,levels
R528	T3538	T3530	acomp	normal,are
R529	T3382	T3374	punct	", ",show
R530	T3539	T3540	punct	[,1
R531	T3540	T3530	parataxis	1,are
R532	T3383	T3384	amod	variable,degrees
R533	T3541	T3540	punct	],1
R534	T3542	T3530	punct	.,are
R535	T3384	T3374	dobj	degrees,show
R536	T3544	T3545	det	The,incidence
R537	T3545	T3547	nsubj	incidence,is
R538	T3546	T3545	amod	overall,incidence
R539	T3385	T3384	prep	of,degrees
R540	T3548	T3545	prep	of,incidence
R541	T3386	T3387	compound	enzyme,deficiency
R542	T3549	T3548	pobj	MSUD,of
R543	T3550	T3545	prep	in,incidence
R544	T3551	T3552	det	the,population
R545	T3552	T3550	pobj	population,in
R546	T3553	T3552	amod	general,population
R547	T3387	T3385	pobj	deficiency,of
R548	T3554	T3555	nummod	1,"185,000"
R549	T3555	T3547	attr	"185,000",is
R550	T3556	T3555	punct	:,"185,000"
R551	T3388	T3387	acl	leading,deficiency
R552	T3557	T3558	punct	[,1
R553	T3558	T3547	parataxis	1,is
R554	T3559	T3558	punct	],1
R555	T3389	T3388	prep	to,leading
R556	T3560	T3547	punct	", ",is
R557	T3561	T3547	cc	and,is
R558	T3562	T3563	prep	in,estimated
R559	T3390	T3391	amod	several,phenotypes
R560	T3563	T3547	conj	estimated,is
R561	T3391	T3389	pobj	phenotypes,to
R562	T3564	T3565	amod	certain,groups
R563	T3565	T3562	pobj	groups,in
R564	T3566	T3565	compound	population,groups
R565	T3392	T3391	amod	different,phenotypes
R566	T3567	T3565	punct	", ",groups
R567	T3568	T3569	amod	such,as
R568	T3569	T3565	prep	as,groups
R569	T3570	T3569	pobj	Mennonites,as
R570	T3393	T3391	amod	clinical,phenotypes
R571	T3571	T3570	prep	of,Mennonites
R572	T3572	T3571	pobj	Pennsylvania,of
R573	T3394	T3395	punct	[,1
R574	T3573	T3563	punct	", ",estimated
R575	T3574	T3575	det	the,incidence
R576	T3575	T3563	nsubjpass	incidence,estimated
R577	T3576	T3563	auxpass	is,estimated
R578	T3395	T3374	parataxis	1,show
R579	T3577	T3578	aux	to,be
R580	T3578	T3563	xcomp	be,estimated
R581	T3396	T3395	punct	],1
R582	T3579	T3578	prep	as,be
R583	T3580	T3579	amod	high,as
R584	T3581	T3580	prep	as,high
R585	T3397	T3374	punct	.,show
R586	T3582	T3583	nummod	1,176
R587	T3583	T3581	pobj	176,as
R588	T3584	T3583	punct	:,176
R589	T3399	T3400	advmod	Approximately,75
R590	T3585	T3586	punct	[,2
R591	T3586	T3563	parataxis	2,estimated
R592	T3587	T3586	punct	],2
R593	T3588	T3563	punct	.,estimated
R594	T3400	T3401	nummod	75,%
R595	T3590	T3591	det	The,complex
R596	T3401	T3402	nsubj	%,have
R597	T3591	T3593	nsubj	complex,consists
R598	T3592	T3591	compound	BCKDH,complex
R599	T3594	T3591	punct	", ",complex
R600	T3595	T3596	det	the,enzyme
R601	T3596	T3591	appos	enzyme,complex
R602	T3403	T3401	prep	of,%
R603	T3597	T3596	amod	deficient,enzyme
R604	T3598	T3596	prep	in,enzyme
R605	T3599	T3598	pobj	MSUD,in
R606	T3600	T3593	punct	", ",consists
R607	T3601	T3593	prep	of,consists
R608	T3404	T3405	compound	MSUD,patients
R609	T3602	T3603	nummod	three,proteins
R610	T3603	T3601	pobj	proteins,of
R611	T3604	T3603	amod	catalytic,proteins
R612	T3405	T3403	pobj	patients,of
R613	T3605	T3603	punct	", ",proteins
R614	T3606	T3607	det	a,decarboxylase
R615	T3607	T3603	appos	decarboxylase,proteins
R616	T3406	T3407	det	the,form
R617	T3608	T3609	punct	(,E1
R618	T3609	T3607	parataxis	E1,decarboxylase
R619	T3610	T3609	punct	),E1
R620	T3407	T3402	dobj	form,have
R621	T3611	T3607	punct	", ",decarboxylase
R622	T3612	T3613	det	a,transacylase
R623	T3408	T3407	amod	classic,form
R624	T3613	T3607	conj	transacylase,decarboxylase
R625	T3614	T3613	compound	dihydrolipoyl,transacylase
R626	T3615	T3616	punct	(,E2
R627	T3409	T3407	prep	of,form
R628	T3616	T3613	parataxis	E2,transacylase
R629	T3617	T3616	punct	),E2
R630	T3618	T3613	punct	", ",transacylase
R631	T3410	T3411	det	the,disease
R632	T3619	T3613	cc	and,transacylase
R633	T3620	T3621	det	a,dehydrogenase
R634	T3621	T3613	conj	dehydrogenase,transacylase
R635	T3622	T3621	compound	dihydrolipoyl,dehydrogenase
R636	T3411	T3409	pobj	disease,of
R637	T3623	T3624	punct	(,E3
R638	T3624	T3621	parataxis	E3,dehydrogenase
R639	T3625	T3624	punct	),E3
R640	T3412	T3407	prep	with,form
R641	T3626	T3593	punct	.,consists
R642	T3413	T3414	compound	BCKDH,activity
R644	T3629	T3631	nsubj	component,is
R645	T3630	T3629	compound	E1,component
R646	T3414	T3412	pobj	activity,with
R647	T3632	T3633	det	a,heterotetramer
R648	T3633	T3631	attr	heterotetramer,is
R649	T3415	T3414	prep	in,activity
R650	T3416	T3417	det	the,range
R651	T3634	T3633	acl	composed,heterotetramer
R652	T3417	T3415	pobj	range,in
R653	T3635	T3634	prep	of,composed
R654	T3636	T3637	nummod	two,α
R655	T3637	T3638	nmod	α,subunits
R656	T3418	T3417	prep	of,range
R657	T3638	T3635	pobj	subunits,of
R658	T3639	T3637	cc	and,α
R659	T3419	T3420	quantmod	0,2
R660	T3640	T3641	nummod	two,β
R661	T3641	T3637	conj	β,α
R662	T3642	T3643	punct	[,3
R663	T3420	T3422	nummod	2,%
R664	T3643	T3631	parataxis	3,is
R665	T3644	T3643	punct	],3
R666	T3645	T3631	punct	.,is
R667	T3421	T3420	punct	–,2
R668	T3647	T3648	det	The,components
R669	T3422	T3418	pobj	%,of
R670	T3648	T3652	nsubj	components,are
R671	T3649	T3648	nmod	E1,components
R672	T3650	T3649	cc	and,E1
R673	T3739	T3737	conj	E2,E1
R674	T3651	T3649	conj	E2,E1
R675	T3653	T3652	acomp	specific,are
R676	T3654	T3653	prep	to,specific
R677	T3655	T3654	pobj	BCKDH,to
R678	T3740	T3736	prep	of,subunits
R679	T3656	T3652	punct	", ",are
R680	T3657	T3658	mark	whereas,used
R681	T3658	T3652	advcl	used,are
R682	T3741	T3740	pobj	BCKDH,of
R683	T3659	T3658	nsubjpass	E3,used
R684	T3660	T3658	auxpass	is,used
R685	T3661	T3658	advmod	also,used
R686	T3742	T3730	aux	have,described
R687	T3662	T3658	agent	by,used
R688	T3663	T3664	nmod	pyruvate,complexes
R689	T3664	T3662	pobj	complexes,by
R690	T3743	T3730	auxpass	been,described
R691	T3665	T3663	cc	and,pyruvate
R692	T3666	T3667	compound	α,ketoglutarate
R693	T3745	T3744	punct	", ",are
R694	T3667	T3663	conj	ketoglutarate,pyruvate
R695	T3668	T3667	punct	-,ketoglutarate
R696	T3669	T3664	compound	dehydrogenase,complexes
R697	T3670	T3671	punct	[,3
R698	T3671	T3664	parataxis	3,complexes
R699	T3746	T3744	advmod	however,are
R700	T3672	T3671	punct	],3
R701	T3673	T3664	cc	and,complexes
R702	T3674	T3675	det	the,system
R703	T3675	T3664	conj	system,complexes
R704	T3676	T3677	compound	glycine,cleavage
R705	T3677	T3675	compound	cleavage,system
R706	T3678	T3679	punct	[,4
R707	T3747	T3744	punct	", ",are
R708	T3679	T3675	parataxis	4,system
R709	T3680	T3679	punct	],4
R710	T3681	T3652	punct	.,are
R711	T3748	T3749	det	the,majority
R712	T3683	T3684	nsubjpass	BCKDH,associated
R713	T3749	T3744	nsubj	majority,are
R714	T3685	T3684	auxpass	is,associated
R715	T3686	T3684	advmod	also,associated
R716	T3750	T3749	prep	of,majority
R717	T3687	T3684	prep	with,associated
R718	T3688	T3689	nummod	two,proteins
R719	T3689	T3687	pobj	proteins,with
R720	T3751	T3752	compound	MSUD,mutations
R721	T3690	T3689	amod	regulatory,proteins
R722	T3691	T3689	punct	", ",proteins
R723	T3692	T3693	det	a,kinase
R724	T3693	T3689	appos	kinase,proteins
R725	T3752	T3750	pobj	mutations,of
R726	T3694	T3693	amod	specific,kinase
R727	T3695	T3693	cc	and,kinase
R728	T3753	T3752	acl	identified,mutations
R729	T3696	T3697	det	a,phosphatase
R730	T3697	T3693	conj	phosphatase,kinase
R731	T3698	T3699	dep	which,regulate
R732	T3699	T3689	relcl	regulate,proteins
R733	T3754	T3755	advmod	thus,far
R734	T3700	T3701	det	the,activity
R735	T3701	T3699	dobj	activity,regulate
R736	T3702	T3701	prep	of,activity
R737	T3755	T3753	advmod	far,identified
R738	T3703	T3704	det	this,enzyme
R739	T3704	T3702	pobj	enzyme,of
R740	T3705	T3699	prep	through,regulate
R741	T3756	T3744	prep	in,are
R742	T3706	T3707	det	a,cycle
R743	T3707	T3705	pobj	cycle,through
R744	T3757	T3758	det	the,subunit
R745	T3708	T3707	nmod	phosphorylation,cycle
R746	T3709	T3710	punct	(,inactivation
R747	T3710	T3708	parataxis	inactivation,phosphorylation
R748	T3758	T3756	pobj	subunit,in
R749	T3711	T3710	punct	),inactivation
R750	T3712	T3708	cc	and,phosphorylation
R751	T3713	T3708	conj	dephosphorylation,phosphorylation
R752	T3759	T3758	compound	E2,subunit
R753	T3714	T3715	punct	(,activation
R754	T3715	T3713	parataxis	activation,dephosphorylation
R755	T3716	T3715	punct	),activation
R756	T3717	T3707	prep	of,cycle
R757	T3718	T3719	det	the,subunit
R758	T3719	T3717	pobj	subunit,of
R759	T3760	T3761	punct	[,7
R760	T3720	T3719	compound	E1,subunit
R761	T3721	T3719	compound	α,subunit
R762	T3722	T3723	punct	[,6
R763	T3761	T3744	parataxis	7,are
R764	T3723	T3684	parataxis	6,associated
R765	T3762	T3761	nummod	1,7
R766	T3724	T3723	nummod	5,6
R767	T3725	T3723	punct	",",6
R768	T3726	T3723	punct	],6
R769	T3763	T3761	punct	",",7
R770	T3727	T3684	punct	.,associated
R771	T3764	T3761	punct	],7
R772	T3765	T3744	punct	.,are
R773	T3767	T3768	prep	To,associated
R774	T3729	T3730	nsubjpass	Mutations,described
R775	T3730	T3744	ccomp	described,are
R776	T3731	T3729	prep	in,Mutations
R777	T3769	T3767	pobj	date,To
R778	T3732	T3733	det	the,genes
R779	T3733	T3731	pobj	genes,in
R780	T3734	T3733	prep	of,genes
R781	T3735	T3736	det	the,subunits
R782	T3770	T3768	punct	", ",associated
R783	T3736	T3734	pobj	subunits,of
R784	T3737	T3736	nmod	E1,subunits
R785	T3738	T3737	cc	and,E1
R786	T3771	T3768	nsubjpass	cases,associated
R787	T3772	T3771	prep	of,cases
R788	T3773	T3772	pobj	MSUD,of
R789	T3845	T3843	pobj	spite,In
R790	T3774	T3768	aux	have,associated
R791	T3846	T3845	prep	of,spite
R792	T3847	T3848	amod	dietary,intervention
R793	T3775	T3768	neg	not,associated
R794	T3848	T3846	pobj	intervention,of
R795	T3849	T3844	punct	", ",is
R796	T3850	T3844	expl	there,is
R797	T3776	T3768	auxpass	been,associated
R798	T3851	T3852	amod	significant,mortality
R799	T3852	T3844	attr	mortality,is
R800	T3777	T3768	prep	with,associated
R801	T3853	T3852	acl	associated,mortality
R802	T3854	T3853	prep	with,associated
R803	T3778	T3777	pobj	defects,with
R804	T3855	T3854	pobj	MSUD,with
R805	T3856	T3844	cc	and,is
R806	T3857	T3858	expl	there,is
R807	T3858	T3844	conj	is,is
R808	T3859	T3860	det	a,incidence
R809	T3860	T3858	attr	incidence,is
R810	T3779	T3778	prep	in,defects
R811	T3861	T3860	amod	high,incidence
R812	T3862	T3860	prep	of,incidence
R813	T3863	T3864	amod	mental,retardation
R814	T3864	T3862	pobj	retardation,of
R815	T3780	T3781	det	the,kinase
R816	T3865	T3858	prep	in,is
R817	T3866	T3865	pobj	survivors,in
R818	T3867	T3868	punct	[,9
R819	T3781	T3779	pobj	kinase,in
R820	T3868	T3858	parataxis	9,is
R821	T3869	T3868	punct	],9
R822	T3870	T3844	punct	.,is
R823	T3782	T3781	amod	regulatory,kinase
R824	T3872	T3873	prep	Because,treated
R825	T3783	T3781	cc	and,kinase
R826	T3874	T3872	pcomp	of,Because
R827	T3875	T3876	det	the,role
R828	T3784	T3781	conj	phosphatase,kinase
R829	T3876	T3872	pobj	role,Because
R830	T3877	T3876	amod	central,role
R831	T3878	T3876	prep	of,role
R832	T3785	T3786	punct	[,1
R833	T3879	T3880	det	the,liver
R834	T3880	T3878	pobj	liver,of
R835	T3881	T3876	prep	in,role
R836	T3786	T3768	parataxis	1,associated
R837	T3882	T3883	compound	amino,acid
R838	T3883	T3884	compound	acid,metabolism
R839	T3884	T3881	pobj	metabolism,in
R840	T3787	T3786	punct	],1
R841	T3885	T3876	cc	and,role
R842	T3886	T3887	amod	moderate,high
R843	T3887	T3889	amod	high,levels
R844	T3788	T3768	punct	.,associated
R845	T3888	T3887	punct	/,high
R846	T3889	T3876	conj	levels,role
R847	T3890	T3889	prep	of,levels
R848	T3790	T3791	amod	Current,management
R849	T3891	T3892	compound	BCKDH,activity
R850	T3892	T3890	pobj	activity,of
R851	T3893	T3892	prep	in,activity
R852	T3894	T3895	amod	human,liver
R853	T3791	T3792	nsubj	management,relies
R854	T3895	T3893	pobj	liver,in
R855	T3793	T3791	prep	of,management
R856	T3896	T3897	punct	[,10
R857	T3794	T3795	compound	MSUD,patients
R858	T3897	T3889	parataxis	10,levels
R859	T3898	T3899	punct	-,12
R860	T3899	T3897	prep	12,10
R861	T3900	T3897	punct	],10
R862	T3901	T3873	punct	", ",treated
R863	T3902	T3903	det	a,cases
R864	T3795	T3793	pobj	patients,of
R865	T3903	T3873	nsubjpass	cases,treated
R866	T3904	T3903	amod	few,cases
R867	T3796	T3792	prep	on,relies
R868	T3905	T3903	prep	of,cases
R869	T3906	T3905	pobj	MSUD,of
R870	T3907	T3873	aux	have,treated
R871	T3797	T3798	det	a,restriction
R872	T3908	T3873	advmod	recently,treated
R873	T3909	T3873	auxpass	been,treated
R874	T3910	T3873	prep	by,treated
R875	T3798	T3796	pobj	restriction,on
R876	T3911	T3912	compound	liver,transplantation
R877	T3799	T3798	amod	strict,restriction
R878	T3912	T3910	pobj	transplantation,by
R879	T3800	T3798	amod	lifelong,restriction
R880	T3913	T3914	punct	[,13
R881	T3801	T3798	amod	dietary,restriction
R882	T3914	T3873	parataxis	13,treated
R883	T3915	T3916	punct	-,16
R884	T3916	T3914	prep	16,13
R885	T3802	T3798	prep	of,restriction
R886	T3917	T3914	punct	],13
R887	T3918	T3873	punct	.,treated
R888	T3803	T3802	pobj	protein,of
R889	T3920	T3921	mark	While,is
R890	T3921	T3930	advcl	is,known
R891	T3922	T3923	det	the,outcome
R892	T3804	T3803	cc	or,protein
R893	T3923	T3921	nsubj	outcome,is
R894	T3924	T3925	amod	short,term
R895	T3925	T3923	compound	term,outcome
R896	T3805	T3803	conj	BCAA,protein
R897	T3926	T3925	punct	-,term
R898	T3927	T3923	prep	of,outcome
R899	T3928	T3929	compound	liver,transplantation
R900	T3806	T3807	punct	[,8
R901	T3929	T3927	pobj	transplantation,of
R902	T3931	T3921	acomp	encouraging,is
R903	T3807	T3792	parataxis	8,relies
R904	T3932	T3930	punct	", ",known
R905	T3933	T3934	amod	long,term
R906	T3934	T3936	compound	term,effects
R907	T3808	T3807	nummod	1,8
R908	T3935	T3934	punct	-,term
R909	T3936	T3930	nsubjpass	effects,known
R910	T3809	T3807	punct	",",8
R911	T3937	T3936	prep	of,effects
R912	T3938	T3939	det	this,approach
R913	T3939	T3937	pobj	approach,of
R914	T3940	T3930	auxpass	are,known
R915	T3941	T3930	neg	not,known
R916	T3942	T3930	punct	.,known
R917	T3810	T3807	punct	],8
R918	T3944	T3945	advmod	However,required
R919	T3946	T3945	punct	", ",required
R920	T3811	T3792	punct	.,relies
R921	T3947	T3948	det	these,patients
R922	T3948	T3945	nsubjpass	patients,required
R923	T3949	T3945	auxpass	are,required
R924	T3813	T3814	predet	Such,management
R925	T3950	T3945	advmod	now,required
R926	T3814	T3817	nsubj	management,is
R927	T3815	T3814	det	a,management
R928	T3951	T3952	aux	to,take
R929	T3952	T3945	xcomp	take,required
R930	T3953	T3954	compound	immunosuppressant,drugs
R931	T3816	T3814	amod	dietary,management
R932	T3954	T3952	dobj	drugs,take
R933	T3955	T3952	prep	for,take
R934	T3818	T3814	prep	of,management
R935	T3956	T3957	det	the,rest
R936	T3957	T3955	pobj	rest,for
R937	T3958	T3957	prep	of,rest
R938	T3959	T3960	poss	their,lives
R939	T3819	T3820	det	the,disease
R940	T3960	T3958	pobj	lives,of
R941	T3961	T3952	punct	", ",take
R942	T3962	T3963	advmod	often,with
R943	T3820	T3818	pobj	disease,of
R944	T3963	T3952	prep	with,take
R945	T3964	T3965	amod	undesirable,effects
R946	T3965	T3963	pobj	effects,with
R947	T3821	T3817	punct	", ",is
R948	T3966	T3965	compound	side,effects
R949	T3967	T3945	punct	.,required
R950	T3822	T3817	advmod	however,is
R951	T3969	T3970	advmod	Moreover,are
R952	T3823	T3817	punct	", ",is
R953	T3971	T3970	punct	", ",are
R954	T3972	T3973	det	the,cost
R955	T3973	T3970	nsubj	cost,are
R956	T3824	T3817	neg	not,is
R957	T3974	T3973	acl	associated,cost
R958	T3975	T3974	prep	with,associated
R959	T3976	T3977	compound	liver,transplantation
R960	T3825	T3826	advmod	entirely,satisfactory
R961	T3977	T3975	pobj	transplantation,with
R962	T3978	T3973	cc	and,cost
R963	T3979	T3980	det	the,availability
R964	T3980	T3973	conj	availability,cost
R965	T3981	T3980	prep	of,availability
R966	T3826	T3817	acomp	satisfactory,is
R967	T3827	T3828	advmod	especially,in
R968	T3982	T3983	compound	donor,livers
R969	T3828	T3817	prep	in,is
R970	T3983	T3981	pobj	livers,of
R971	T3984	T3985	amod	additional,factors
R972	T3829	T3828	pobj	times,in
R973	T3985	T3970	attr	factors,are
R974	T3986	T3985	amod	limiting,factors
R975	T3987	T3985	prep	for,factors
R976	T3830	T3829	prep	of,times
R977	T3988	T3989	det	the,practicality
R978	T3989	T3987	pobj	practicality,for
R979	T3990	T3989	prep	of,practicality
R980	T3831	T3832	amod	metabolic,decompensation
R981	T3991	T3990	pobj	treatment,of
R982	T3992	T3991	prep	of,treatment
R983	T3832	T3830	pobj	decompensation,of
R984	T3993	T3994	det	this,disease
R985	T3994	T3992	pobj	disease,of
R986	T3833	T3832	prep	due,decompensation
R989	T3834	T3833	pcomp	to,due
R990	T3999	T3997	pcomp	of,Because
R991	T3835	T3833	pobj	infection,due
R992	T4000	T4001	det	the,options
R994	T3836	T3835	punct	", ",infection
R995	T4002	T4001	amod	current,options
R996	T4003	T4001	amod	unsatisfactory,options
R997	T4004	T4001	prep	for,options
R998	T4005	T4006	det	the,treatment
R999	T3837	T3835	conj	injuries,infection
R1000	T4006	T4004	pobj	treatment,for
R1001	T4007	T4006	prep	of,treatment
R1002	T3838	T3837	cc	and,injuries
R1003	T4008	T4007	pobj	MSUD,of
R1004	T4009	T3998	punct	", ",is
R1005	T4010	T3998	expl	there,is
R1006	T3839	T3840	amod	other,stressors
R1007	T4011	T4012	det	a,need
R1008	T4012	T3998	attr	need,is
R1009	T4013	T4012	prep	for,need
R1010	T4014	T4015	amod	improved,therapies
R1011	T3840	T3837	conj	stressors,injuries
R1012	T4015	T4013	pobj	therapies,for
R1013	T4016	T4017	aux	to,combat
R1014	T3841	T3817	punct	.,is
R1015	T4017	T4015	advcl	combat,therapies
R1016	T4018	T4019	det	this,disease
R1017	T4019	T4017	dobj	disease,combat
R1018	T4020	T3998	punct	.,is
R1019	T3843	T3844	prep	In,is
R1020	T4022	T4023	det	An,obstacle
R1021	T4023	T4024	nsubj	obstacle,been
R1022	T4025	T4023	prep	to,obstacle
R1023	T4057	T4058	punct	[,17
R1024	T4026	T4025	pcomp	developing,to
R1025	T4027	T4028	amod	novel,treatments
R1026	T4028	T4026	dobj	treatments,developing
R1027	T4029	T4028	prep	for,treatments
R1028	T4030	T4029	pobj	MSUD,for
R1029	T4031	T4024	aux	has,been
R1030	T4058	T4047	parataxis	17,described
R1031	T4032	T4033	det	the,lack
R1032	T4033	T4024	attr	lack,been
R1033	T4034	T4033	prep	of,lack
R1034	T4059	T4060	punct	-,19
R1035	T4035	T4036	det	a,model
R1036	T4036	T4034	pobj	model,of
R1037	T4037	T4036	amod	suitable,model
R1038	T4038	T4036	compound	animal,model
R1039	T4060	T4058	prep	19,17
R1040	T4039	T4040	aux	to,perform
R1041	T4040	T4036	advcl	perform,model
R1042	T4041	T4042	amod	necessary,studies
R1043	T4061	T4058	punct	],17
R1044	T4042	T4040	dobj	studies,perform
R1045	T4043	T4042	amod	preclinical,studies
R1046	T4044	T4024	punct	.,been
R1047	T4062	T4056	punct	", ",is
R1048	T4046	T4047	mark	Although,described
R1049	T4047	T4056	advcl	described,is
R1050	T4063	T4064	det	this,model
R1051	T4048	T4049	det	a,model
R1052	T4049	T4047	nsubjpass	model,described
R1053	T4050	T4051	compound	Hereford,calf
R1054	T4064	T4056	nsubj	model,is
R1055	T4051	T4049	compound	calf,model
R1056	T4052	T4049	prep	with,model
R1057	T4053	T4052	pobj	MSUD,with
R1058	T4065	T4066	preconj	neither,available
R1059	T4054	T4047	aux	has,described
R1060	T4055	T4047	auxpass	been,described
R1061	T4066	T4056	acomp	available,is
R1062	T4067	T4066	advmod	readily,available
R1063	T4068	T4066	cc	nor,available
R1064	T4069	T4066	conj	practical,available
R1065	T4162	T4156	punct	(,aminotransferase
R1066	T4070	T4071	aux	to,perform
R1067	T4163	T4156	appos	BCAT,aminotransferase
R1068	T4164	T4161	punct	),gene
R1069	T4165	T4154	punct	", ",in
R1070	T4166	T4154	neg	not,in
R1071	T4167	T4154	prep	in,in
R1072	T4071	T4069	xcomp	perform,practical
R1073	T4168	T4167	pobj	BCKDH,in
R1074	T4169	T4168	punct	", ",BCKDH
R1075	T4072	T4073	amod	preclinical,studies
R1076	T4170	T4171	det	the,enzyme
R1077	T4171	T4168	appos	enzyme,BCKDH
R1078	T4172	T4171	amod	deficient,enzyme
R1079	T4173	T4171	prep	in,enzyme
R1080	T4073	T4071	dobj	studies,perform
R1081	T4174	T4173	pobj	MSUD,in
R1082	T4175	T4144	punct	.,disrupts
R1083	T4074	T4056	punct	.,is
R1084	T4177	T4178	mark	Because,is
R1085	T4178	T4181	advcl	is,is
R1086	T4076	T4077	advmod	Furthermore,shown
R1087	T4179	T4180	det	the,mutation
R1088	T4180	T4178	nsubj	mutation,is
R1089	T4182	T4178	neg	not,is
R1090	T4078	T4077	punct	", ",shown
R1091	T4183	T4178	prep	in,is
R1092	T4184	T4183	pobj	BCKDH,in
R1093	T4185	T4181	punct	", ",is
R1094	T4186	T4187	det	the,validity
R1095	T4187	T4181	nsubj	validity,is
R1096	T4079	T4077	nsubj	comparison,shown
R1097	T4188	T4187	prep	of,validity
R1098	T4189	T4190	det	this,line
R1099	T4190	T4188	pobj	line,of
R1100	T4191	T4190	compound	mutant,line
R1101	T4080	T4079	prep	of,comparison
R1102	T4192	T4190	compound	mouse,line
R1103	T4193	T4187	prep	for,validity
R1104	T4194	T4195	amod	modeling,MSUD
R1105	T4081	T4082	det	this,model
R1106	T4195	T4193	pobj	MSUD,for
R1107	T4196	T4195	amod	human,MSUD
R1108	T4197	T4181	acomp	questionable,is
R1109	T4082	T4080	pobj	model,of
R1110	T4198	T4181	punct	.,is
R1111	T4200	T4201	det	The,objective
R1112	T4083	T4082	compound	animal,model
R1113	T4201	T4202	nsubj	objective,was
R1114	T4203	T4201	prep	of,objective
R1115	T4084	T4082	prep	with,model
R1116	T4204	T4205	det	the,study
R1117	T4205	T4203	pobj	study,of
R1118	T4206	T4205	amod	present,study
R1119	T4085	T4086	amod	human,MSUD
R1120	T4207	T4208	aux	to,create
R1121	T4208	T4202	xcomp	create,was
R1122	T4209	T4210	advmod	genetically,engineered
R1123	T4210	T4211	amod	engineered,models
R1124	T4211	T4208	dobj	models,create
R1125	T4212	T4211	amod	murine,models
R1126	T4086	T4084	pobj	MSUD,with
R1127	T4213	T4211	prep	of,models
R1128	T4214	T4213	pobj	MSUD,of
R1129	T4087	T4077	aux	has,shown
R1130	T4215	T4216	dep	that,mimic
R1131	T4216	T4211	relcl	mimic,models
R1132	T4217	T4218	det	the,pathology
R1133	T4088	T4089	det	some,differences
R1134	T4218	T4216	dobj	pathology,mimic
R1135	T4219	T4218	prep	of,pathology
R1136	T4220	T4221	det	the,forms
R1137	T4221	T4219	pobj	forms,of
R1138	T4089	T4077	dobj	differences,shown
R1139	T4222	T4221	amod	classic,forms
R1140	T4223	T4222	cc	and,classic
R1141	T4224	T4222	conj	intermediate,classic
R1142	T4090	T4089	prep	in,differences
R1143	T4225	T4221	amod	variant,forms
R1144	T4226	T4221	prep	of,forms
R1145	T4091	T4092	det	the,pathology
R1146	T4227	T4228	det	the,disease
R1147	T4228	T4226	pobj	disease,of
R1148	T4229	T4228	amod	human,disease
R1149	T4092	T4090	pobj	pathology,in
R1150	T4230	T4202	punct	.,was
R1151	T4232	T4233	det	The,model
R1152	T4093	T4092	prep	of,pathology
R1153	T4233	T4235	nsubjpass	model,created
R1154	T4234	T4233	amod	classic,model
R1155	T4094	T4095	det	the,disease
R1156	T4236	T4235	auxpass	was,created
R1157	T4237	T4235	prep	by,created
R1158	T4095	T4093	pobj	disease,of
R1159	T4238	T4239	amod	targeted,inactivation
R1160	T4239	T4237	pobj	inactivation,by
R1161	T4240	T4239	prep	of,inactivation
R1162	T4096	T4097	punct	[,1
R1163	T4097	T4077	parataxis	1,shown
R1164	T4241	T4242	det	the,subunit
R1165	T4098	T4097	punct	],1
R1166	T4242	T4240	pobj	subunit,of
R1167	T4243	T4242	compound	E2,subunit
R1168	T4099	T4077	punct	", ",shown
R1169	T4244	T4242	prep	of,subunit
R1170	T4245	T4244	pobj	BCKDH,of
R1171	T4246	T4239	prep	by,inactivation
R1172	T4100	T4077	advcl	making,shown
R1173	T4247	T4248	amod	homologous,recombination
R1174	T4248	T4246	pobj	recombination,by
R1175	T4249	T4239	prep	in,inactivation
R1176	T4250	T4251	nmod	embryonic,ES
R1177	T4251	T4254	nmod	ES,cells
R1178	T4101	T4102	det	this,animal
R1179	T4252	T4251	nmod	stem,ES
R1180	T4253	T4251	punct	(,ES
R1181	T4102	T4103	nsubj	animal,model
R1182	T4254	T4249	pobj	cells,in
R1183	T4255	T4254	punct	),cells
R1184	T4256	T4235	punct	.,created
R1185	T4103	T4100	ccomp	model,making
R1186	T4258	T4259	det	The,model
R1187	T4259	T4260	nsubjpass	model,created
R1188	T4104	T4103	det	a,model
R1189	T4261	T4259	prep	of,model
R1190	T4262	T4263	amod	intermediate,MSUD
R1191	T4105	T4106	advmod	less,desirable
R1192	T4263	T4261	pobj	MSUD,of
R1193	T4264	T4260	auxpass	was,created
R1194	T4265	T4260	prep	by,created
R1195	T4106	T4103	amod	desirable,model
R1196	T4266	T4267	amod	partial,rescue
R1197	T4267	T4265	pobj	rescue,by
R1198	T4107	T4103	prep	for,model
R1199	T4108	T4109	det	the,disease
R1200	T4268	T4267	amod	transgenic,rescue
R1201	T4269	T4267	prep	of,rescue
R1202	T4109	T4107	pobj	disease,for
R1203	T4270	T4271	det	the,knockout
R1204	T4271	T4269	pobj	knockout,of
R1205	T4110	T4109	amod	human,disease
R1206	T4272	T4271	compound	E2,knockout
R1207	T4273	T4271	compound	gene,knockout
R1208	T4274	T4260	punct	.,created
R1209	T4111	T4077	punct	.,shown
R1210	T4276	T4277	det	This,report
R1211	T4277	T4278	nsubj	report,describes
R1212	T4113	T4114	advmod	Recently,described
R1213	T4279	T4280	det	the,generation
R1214	T4280	T4278	dobj	generation,describes
R1215	T4281	T4280	cc	and,generation
R1216	T4282	T4280	conj	characterization,generation
R1217	T4115	T4114	punct	", ",described
R1218	T4283	T4280	prep	of,generation
R1219	T4284	T4285	det	these,models
R1220	T4285	T4283	pobj	models,of
R1221	T4286	T4285	amod	murine,models
R1222	T4116	T4117	det	a,nitrosourea
R1223	T4287	T4285	prep	of,models
R1224	T4288	T4287	pobj	MSUD,of
R1225	T4289	T4278	punct	.,describes
R1226	T4291	T4292	det	These,models
R1227	T4117	T4124	npadvmod	nitrosourea,induced
R1228	T4292	T4293	nsubj	models,allow
R1229	T4294	T4293	aux	will,allow
R1230	T4295	T4293	prep	for,allow
R1231	T4118	T4119	compound	N,ethyl
R1232	T4296	T4297	det	the,development
R1233	T4297	T4295	pobj	development,for
R1234	T4298	T4297	prep	of,development
R1235	T4119	T4117	compound	ethyl,nitrosourea
R1236	T4299	T4300	amod	novel,approaches
R1237	T4300	T4298	pobj	approaches,of
R1238	T4301	T4300	compound	treatment,approaches
R1239	T4120	T4119	punct	-,ethyl
R1240	T4302	T4300	punct	", ",approaches
R1241	T4303	T4304	amod	such,as
R1242	T4304	T4300	prep	as,approaches
R1243	T4121	T4117	punct	-,nitrosourea
R1244	T4305	T4306	nmod	gene,therapies
R1245	T4306	T4304	pobj	therapies,as
R1246	T4307	T4305	cc	or,gene
R1247	T4122	T4117	compound	N,nitrosourea
R1248	T4308	T4309	compound	stem,cell
R1249	T4309	T4305	conj	cell,gene
R1250	T4310	T4293	punct	", ",allow
R1251	T4311	T4312	aux	to,cure
R1252	T4123	T4117	punct	-,nitrosourea
R1253	T4312	T4293	advcl	cure,allow
R1254	T4313	T4312	advmod	ultimately,cure
R1255	T4314	T4312	dobj	MSUD,cure
R1256	T4124	T4129	amod	induced,mouse
R1257	T4315	T4293	punct	.,allow
R1258	T4125	T4117	punct	(,nitrosourea
R1259	T4126	T4117	appos	ENU,nitrosourea
R1260	T4127	T4124	punct	),induced
R1261	T4128	T4124	punct	-,induced
R1262	T4129	T4114	nsubjpass	mouse,described
R1263	T4130	T4129	compound	mutant,mouse
R1264	T4131	T4132	dep	that,resembles
R1265	T4132	T4129	relcl	resembles,mouse
R1266	T4133	T4132	advmod	phenotypically,resembles
R1267	T4134	T4135	amod	human,MSUD
R1268	T4135	T4132	dobj	MSUD,resembles
R1269	T4136	T4114	aux	has,described
R1270	T4137	T4114	auxpass	been,described
R1271	T4138	T4139	punct	[,20
R1272	T4139	T4114	parataxis	20,described
R1273	T4140	T4139	punct	],20
R1274	T4141	T4114	punct	.,described
R1275	T4143	T4144	advmod	However,disrupts
R1276	T4145	T4144	punct	", ",disrupts
R1277	T4146	T4147	det	the,mutation
R1278	T4147	T4144	nsubj	mutation,disrupts
R1279	T4148	T4147	prep	in,mutation
R1280	T4149	T4150	det	this,model
R1281	T4150	T4148	pobj	model,in
R1282	T4151	T4152	det	a,site
R1283	T4152	T4144	dobj	site,disrupts
R1284	T4153	T4152	compound	splice,site
R1285	T4154	T4152	prep	in,site
R1286	T4155	T4156	det	the,aminotransferase
R1287	T4156	T4161	nmod	aminotransferase,gene
R1288	T4157	T4156	amod	mitochondrial,aminotransferase
R1289	T4158	T4159	amod	branched,chain
R1290	T4159	T4156	nmod	chain,aminotransferase
R1291	T4160	T4159	punct	-,chain
R1292	T4161	T4154	pobj	gene,in
R1293	T4359	T4360	det	All,studies
R1294	T4360	T4361	nsubjpass	studies,reviewed
R1295	T4362	T4360	acl	involving,studies
R1296	T4363	T4362	dobj	animals,involving
R1297	T4364	T4361	auxpass	were,reviewed
R1298	T4365	T4361	cc	and,reviewed
R1299	T4366	T4361	conj	approved,reviewed
R1300	T4367	T4366	agent	by,approved
R1301	T4368	T4369	det	the,University
R1302	T4369	T4367	pobj	University,by
R1303	T4370	T4369	prep	of,University
R1304	T4371	T4372	poss	Pittsburgh,Committee
R1305	T4372	T4370	pobj	Committee,of
R1306	T4373	T4371	case	's,Pittsburgh
R1307	T4374	T4375	nmod	Institutional,Animal
R1308	T4375	T4376	nmod	Animal,Care
R1309	T4376	T4372	nmod	Care,Committee
R1310	T4377	T4376	cc	and,Care
R1311	T4378	T4376	conj	Use,Care
R1312	T4379	T4361	punct	.,reviewed
R1313	T5027	T5028	compound	Gene,knockout
R1314	T5028	T5029	compound	knockout,production
R1315	T5031	T5032	det	A,subclone
R1316	T5032	T5035	nsubjpass	subclone,obtained
R1317	T5033	T5032	amod	genomic,subclone
R1318	T5034	T5032	compound	DNA,subclone
R1319	T5036	T5032	prep	of,subclone
R1320	T5037	T5038	nmod	Strain,DNA
R1321	T5038	T5036	pobj	DNA,of
R1322	T5039	T5040	nummod	129,SvJ
R1323	T5040	T5038	compound	SvJ,DNA
R1324	T5041	T5040	punct	/,SvJ
R1325	T5042	T5043	dep	that,contained
R1326	T5043	T5032	relcl	contained,subclone
R1327	T5044	T5045	det	a,portion
R1328	T5045	T5043	dobj	portion,contained
R1329	T5046	T5045	prep	of,portion
R1330	T5047	T5048	nmod	Exons,4
R1331	T5048	T5046	pobj	4,of
R1332	T5049	T5048	cc	and,4
R1333	T5050	T5048	conj	5,4
R1334	T5051	T5048	prep	of,4
R1335	T5052	T5053	det	the,gene
R1336	T5053	T5051	pobj	gene,of
R1337	T5054	T5053	compound	E2,gene
R1338	T5055	T5053	cc	and,gene
R1339	T5056	T5057	compound	flanking,DNA
R1340	T5057	T5053	conj	DNA,gene
R1341	T5058	T5035	auxpass	was,obtained
R1342	T5059	T5035	prep	from,obtained
R1343	T5060	T5061	det	a,library
R1344	T5061	T5059	pobj	library,from
R1345	T5062	T5063	compound	P1,phage
R1346	T5063	T5061	compound	phage,library
R1347	T5064	T5061	prep	from,library
R1348	T5065	T5066	nmod	Genome,Inc.
R1349	T5066	T5064	pobj	Inc.,from
R1350	T5067	T5066	nmod	Systems,Inc.
R1351	T5068	T5066	punct	", ",Inc.
R1352	T5069	T5066	punct	", ",Inc.
R1353	T5070	T5071	punct	(,Library
R1354	T5071	T5066	poss	Library,Inc.
R1355	T5072	T5073	compound	St.,Louis
R1356	T5073	T5071	dep	Louis,Library
R1357	T5074	T5073	punct	", ",Louis
R1358	T5075	T5073	npadvmod	MO,Louis
R1359	T5076	T5071	punct	;,Library
R1360	T5077	T5071	punct	',Library
R1361	T5078	T5079	nummod	3,Hit
R1362	T5079	T5071	compound	Hit,Library
R1363	T5080	T5079	punct	-,Hit
R1364	T5081	T5082	compound	Mouse,ES
R1365	T5082	T5071	compound	ES,Library
R1366	T5083	T5071	dep	',Library
R1367	T5084	T5071	punct	),Library
R1368	T5085	T5035	punct	.,obtained
R1369	T5087	T5088	det	A,vector
R1370	T5088	T5096	nsubjpass	vector,created
R1371	T5089	T5090	amod	positive,negative
R1372	T5090	T5088	amod	negative,vector
R1373	T5091	T5090	punct	/,negative
R1374	T5092	T5093	compound	replacement,type
R1375	T5093	T5088	compound	type,vector
R1376	T5094	T5095	compound	gene,targeting
R1377	T5095	T5088	compound	targeting,vector
R1378	T5097	T5098	punct	[,21
R1379	T5098	T5088	parataxis	21,vector
R1380	T5099	T5098	punct	],21
R1381	T5100	T5096	auxpass	was,created
R1382	T5101	T5096	prep	by,created
R1383	T5102	T5101	pcomp	replacing,by
R1384	T5103	T5104	det	a,fragment
R1385	T5104	T5102	dobj	fragment,replacing
R1386	T5105	T5106	nummod	1.67,kb
R1387	T5106	T5104	compound	kb,fragment
R1388	T5107	T5108	compound	EcoRV,Smal
R1389	T5108	T5104	compound	Smal,fragment
R1390	T5109	T5108	punct	-,Smal
R1391	T5110	T5111	dep	that,included
R1392	T5111	T5104	relcl	included,fragment
R1393	T5112	T5113	det	a,portion
R1394	T5113	T5111	dobj	portion,included
R1395	T5114	T5113	prep	of,portion
R1396	T5115	T5114	pobj	Exon,of
R1397	T5116	T5115	nummod	4,Exon
R1398	T5117	T5113	cc	and,portion
R1399	T5118	T5113	conj	all,portion
R1400	T5119	T5118	prep	of,all
R1401	T5120	T5119	pobj	Exon,of
R1402	T5121	T5120	nummod	5,Exon
R1403	T5122	T5113	prep	with,portion
R1404	T5123	T5124	det	the,gene
R1405	T5124	T5122	pobj	gene,with
R1406	T5125	T5124	compound	PGKneo,gene
R1407	T5126	T5124	compound	marker,gene
R1408	T5127	T5128	punct	(,See
R1409	T5128	T5124	parataxis	See,gene
R1410	T5129	T5130	compound	Fig.,1A
R1411	T5130	T5128	dobj	1A,See
R1412	T5131	T5128	punct	),See
R1413	T5132	T5124	prep	from,gene
R1414	T5133	T5134	det	the,vector
R1415	T5134	T5132	pobj	vector,from
R1416	T5135	T5134	compound	pPNT,vector
R1417	T5136	T5137	punct	[,22
R1418	T5137	T5111	parataxis	22,included
R1419	T5138	T5137	punct	],22
R1420	T5139	T5096	punct	.,created
R1421	T5141	T5142	det	The,construct
R1422	T5142	T5144	nsubjpass	construct,linearized
R1423	T5143	T5142	compound	targeting,construct
R1424	T5145	T5144	auxpass	was,linearized
R1425	T5146	T5144	prep	with,linearized
R1426	T5147	T5146	pobj	NotI,with
R1427	T5148	T5144	cc	and,linearized
R1428	T5149	T5144	conj	electroporated,linearized
R1429	T5150	T5149	prep	into,electroporated
R1430	T5151	T5152	compound	R1,cells
R1431	T5152	T5150	pobj	cells,into
R1432	T5153	T5152	compound	ES,cells
R1433	T5154	T5155	punct	[,23
R1434	T5155	T5152	parataxis	23,cells
R1435	T5156	T5155	punct	],23
R1436	T5157	T5149	prep	under,electroporated
R1437	T5158	T5157	pobj	conditions,under
R1438	T5159	T5158	acl	described,conditions
R1439	T5160	T5159	advmod	previously,described
R1440	T5161	T5162	punct	[,24
R1441	T5162	T5159	parataxis	24,described
R1442	T5163	T5162	punct	],24
R1443	T5164	T5144	punct	.,linearized
R1444	T5166	T5167	compound	ES,cells
R1445	T5167	T5168	nsubjpass	cells,selected
R1446	T5169	T5168	auxpass	were,selected
R1447	T5170	T5168	prep	with,selected
R1448	T5171	T5170	pobj	G418,with
R1449	T5172	T5173	punct	(,Inc.
R1450	T5173	T5171	parataxis	Inc.,G418
R1451	T5174	T5175	nummod	300,μg
R1452	T5175	T5173	dep	μg,Inc.
R1453	T5176	T5177	punct	/,ml
R1454	T5177	T5175	prep	ml,μg
R1455	T5178	T5173	punct	;,Inc.
R1456	T5179	T5173	compound	Life,Inc.
R1457	T5180	T5173	compound	Technologies,Inc.
R1458	T5181	T5173	punct	", ",Inc.
R1459	T5182	T5173	npadvmod	Gaithersburg,Inc.
R1460	T5183	T5173	punct	", ",Inc.
R1461	T5184	T5173	npadvmod	MD,Inc.
R1462	T5185	T5173	punct	),Inc.
R1463	T5186	T5171	cc	and,G418
R1464	T5187	T5171	conj	gancyclovir,G418
R1465	T5188	T5187	punct	(,gancyclovir
R1466	T5189	T5190	nummod	2,μM
R1467	T5190	T5187	nmod	μM,gancyclovir
R1468	T5191	T5187	punct	;,gancyclovir
R1469	T5192	T5187	nmod	gift,gancyclovir
R1470	T5193	T5192	prep	of,gift
R1471	T5194	T5193	pobj	Syntex,of
R1472	T5195	T5194	punct	", ",Syntex
R1473	T5196	T5197	compound	Palo,Alto
R1474	T5197	T5194	npadvmod	Alto,Syntex
R1475	T5198	T5194	punct	", ",Syntex
R1476	T5199	T5194	npadvmod	CA,Syntex
R1477	T5200	T5187	punct	),gancyclovir
R1478	T5201	T5168	punct	.,selected
R1479	T5203	T5204	advmod	Doubly,resistant
R1480	T5204	T5205	amod	resistant,clones
R1481	T5205	T5206	nsubjpass	clones,screened
R1482	T5207	T5206	auxpass	were,screened
R1483	T5208	T5206	prep	for,screened
R1484	T5209	T5210	compound	gene,targeting
R1485	T5210	T5208	pobj	targeting,for
R1486	T5211	T5206	prep	by,screened
R1487	T5212	T5213	compound	Southern,blot
R1488	T5213	T5214	compound	blot,analysis
R1489	T5214	T5211	pobj	analysis,by
R1490	T5215	T5214	prep	of,analysis
R1491	T5216	T5217	nmod	BglI,DNA
R1492	T5217	T5215	pobj	DNA,of
R1493	T5218	T5217	amod	digested,DNA
R1494	T5219	T5217	amod	genomic,DNA
R1495	T5220	T5206	punct	.,screened
R1496	T5222	T5223	nsubjpass	Blots,hybridized
R1497	T5224	T5223	auxpass	were,hybridized
R1498	T5225	T5223	prep	with,hybridized
R1499	T5226	T5227	det	an,probe
R1500	T5227	T5225	pobj	probe,with
R1501	T5228	T5229	npadvmod	Exon,specific
R1502	T5229	T5227	amod	specific,probe
R1503	T5230	T5228	nummod	6,Exon
R1504	T5231	T5232	dep	that,was
R1505	T5232	T5227	relcl	was,probe
R1506	T5233	T5232	acomp	external,was
R1507	T5234	T5233	prep	to,external
R1508	T5235	T5236	det	the,construct
R1509	T5236	T5234	pobj	construct,to
R1510	T5237	T5238	compound	gene,targeting
R1511	T5238	T5236	compound	targeting,construct
R1512	T5239	T5223	punct	.,hybridized
R1513	T5241	T5242	advmod	Correctly,targeted
R1514	T5242	T5243	amod	targeted,cells
R1515	T5243	T5245	nsubjpass	cells,injected
R1516	T5244	T5243	compound	ES,cells
R1517	T5246	T5245	auxpass	were,injected
R1518	T5247	T5245	prep	into,injected
R1519	T5248	T5249	compound	C57BL,6J
R1520	T5249	T5251	compound	6J,blastocysts
R1521	T5250	T5249	punct	/,6J
R1522	T5251	T5247	pobj	blastocysts,into
R1523	T5252	T5253	aux	to,produce
R1524	T5253	T5245	advcl	produce,injected
R1525	T5254	T5255	amod	chimeric,mice
R1526	T5255	T5253	dobj	mice,produce
R1527	T5256	T5253	advcl	using,produce
R1528	T5257	T5258	amod	standard,procedures
R1529	T5258	T5256	dobj	procedures,using
R1530	T5259	T5245	punct	.,injected
R1531	T5261	T5262	amod	Heterozygous,offspring
R1532	T5262	T5263	nsubjpass	offspring,intercrossed
R1533	T5264	T5262	prep	from,offspring
R1534	T5265	T5266	npadvmod	germline,competent
R1535	T5266	T5267	amod	competent,chimeras
R1536	T5267	T5264	pobj	chimeras,from
R1537	T5268	T5263	auxpass	were,intercrossed
R1538	T5269	T5270	aux	to,produce
R1539	T5270	T5263	advcl	produce,intercrossed
R1540	T5271	T5272	amod	wild,type
R1541	T5272	T5273	nmod	type,knockout
R1542	T5273	T5288	nmod	knockout,mice
R1543	T5274	T5275	punct	(,+
R1544	T5275	T5272	punct	+,type
R1545	T5276	T5275	punct	+,+
R1546	T5277	T5275	punct	/,+
R1547	T5278	T5275	punct	),+
R1548	T5279	T5272	punct	", ",type
R1549	T5280	T5272	conj	heterozygous,type
R1550	T5281	T5282	punct	(,-
R1551	T5282	T5280	punct	-,heterozygous
R1552	T5283	T5282	punct	+,-
R1553	T5284	T5282	punct	/,-
R1554	T5285	T5282	punct	),-
R1555	T5286	T5280	cc	and,heterozygous
R1556	T5287	T5280	conj	homozygous,heterozygous
R1557	T5288	T5270	dobj	mice,produce
R1558	T5289	T5290	punct	(,-
R1559	T5290	T5273	punct	-,knockout
R1560	T5291	T5290	punct	-,-
R1561	T5292	T5290	punct	/,-
R1562	T5293	T5290	punct	),-
R1563	T5294	T5263	punct	.,intercrossed
R1564	T5296	T5297	prep	At,used
R1565	T5298	T5299	det	all,generations
R1566	T5299	T5296	pobj	generations,At
R1567	T5300	T5297	punct	", ",used
R1568	T5301	T5302	punct	+,-
R1569	T5302	T5304	punct	-,pairs
R1570	T5303	T5302	punct	/,-
R1571	T5304	T5297	nsubjpass	pairs,used
R1572	T5305	T5304	amod	breeding,pairs
R1573	T5306	T5297	auxpass	were,used
R1574	T5307	T5297	punct	.,used
R1575	T5309	T5310	nsubj	Results,are
R1576	T5311	T5309	acl	presented,Results
R1577	T5312	T5311	advmod	here,presented
R1578	T5313	T5310	prep	from,are
R1579	T5314	T5313	pobj	mice,from
R1580	T5315	T5314	acl	derived,mice
R1581	T5316	T5315	prep	from,derived
R1582	T5317	T5318	det	the,generations
R1583	T5318	T5316	pobj	generations,from
R1584	T5319	T5318	nmod	F2,generations
R1585	T5320	T5319	punct	+,F2
R1586	T5321	T5310	punct	.,are
R1587	T5323	T5324	det	All,animals
R1588	T5324	T5325	nsubj	animals,were
R1589	T5326	T5325	prep	of,were
R1590	T5327	T5328	det	a,background
R1591	T5328	T5326	pobj	background,of
R1592	T5329	T5328	amod	mixed,background
R1593	T5330	T5331	nmod	C57BL,6J
R1594	T5331	T5328	nmod	6J,background
R1595	T5332	T5331	punct	/,6J
R1596	T5333	T5331	punct	×,6J
R1597	T5334	T5335	compound	Strain,SvJ
R1598	T5335	T5331	appos	SvJ,6J
R1599	T5336	T5335	compound	129Sv,SvJ
R1600	T5337	T5335	punct	/,SvJ
R1601	T5338	T5328	amod	genetic,background
R1602	T5339	T5325	punct	.,were
R1603	T5873	T5872	prep	of,Production
R1604	T5874	T5875	amod	transgenic,mice
R1605	T5875	T5873	pobj	mice,of
R1606	T5877	T5878	amod	Standard,techniques
R1607	T5878	T5880	nsubjpass	techniques,used
R1608	T5879	T5878	amod	molecular,techniques
R1609	T5881	T5880	auxpass	were,used
R1610	T5882	T5883	aux	to,assemble
R1611	T5883	T5880	advcl	assemble,used
R1612	T5884	T5885	det	the,construct
R1613	T5885	T5883	dobj	construct,assemble
R1614	T5886	T5885	amod	transgenic,construct
R1615	T5887	T5885	punct	", ",construct
R1616	T5888	T5889	compound	pTRE,E2
R1617	T5889	T5885	appos	E2,construct
R1618	T5890	T5889	punct	-,E2
R1619	T5891	T5880	punct	.,used
R1620	T5893	T5894	det	This,transgene
R1621	T5894	T5895	nsubj	transgene,contains
R1622	T5896	T5897	det	the,promoter
R1623	T5897	T5895	dobj	promoter,contains
R1624	T5898	T5897	nmod	tetracycline,promoter
R1625	T5899	T5897	amod	responsive,promoter
R1626	T5900	T5897	nmod	hCMV,promoter
R1627	T5901	T5900	punct	*,hCMV
R1628	T5902	T5900	punct	-,hCMV
R1629	T5903	T5900	nummod	1,hCMV
R1630	T5904	T5897	punct	[,promoter
R1631	T5905	T5897	acl	consisting,promoter
R1632	T5906	T5905	prep	of,consisting
R1633	T5907	T5908	det	the,element
R1634	T5908	T5906	pobj	element,of
R1635	T5909	T5908	nmod	tetracycline,element
R1636	T5910	T5908	amod	responsive,element
R1637	T5911	T5908	punct	(,element
R1638	T5912	T5908	appos	TRE,element
R1639	T5913	T5908	punct	),element
R1640	T5914	T5908	cc	and,element
R1641	T5915	T5916	det	a,promoter
R1642	T5916	T5908	conj	promoter,element
R1643	T5917	T5916	amod	minimal,promoter
R1644	T5918	T5916	compound	hCMV,promoter
R1645	T5919	T5916	punct	],promoter
R1646	T5920	T5921	punct	[,25
R1647	T5921	T5916	parataxis	25,promoter
R1648	T5922	T5921	punct	],25
R1649	T5923	T5916	prep	from,promoter
R1650	T5924	T5923	pobj	pTRE2,from
R1651	T5925	T5926	punct	(,Inc.
R1652	T5926	T5916	parataxis	Inc.,promoter
R1653	T5927	T5926	compound	Clontech,Inc.
R1654	T5928	T5926	punct	", ",Inc.
R1655	T5929	T5930	compound	Mt.,View
R1656	T5930	T5926	npadvmod	View,Inc.
R1657	T5931	T5926	punct	", ",Inc.
R1658	T5932	T5926	npadvmod	CA,Inc.
R1659	T5933	T5926	punct	),Inc.
R1660	T5934	T5897	punct	", ",promoter
R1661	T5935	T5936	det	a,intron
R1662	T5936	T5897	conj	intron,promoter
R1663	T5937	T5936	amod	chimeric,intron
R1664	T5938	T5936	prep	from,intron
R1665	T5939	T5938	pobj	pCI,from
R1666	T5940	T5941	punct	(,Promega
R1667	T5941	T5936	parataxis	Promega,intron
R1668	T5942	T5941	punct	),Promega
R1669	T5943	T5944	aux	to,increase
R1670	T5944	T5936	advcl	increase,intron
R1671	T5945	T5946	compound	message,stability
R1672	T5946	T5944	dobj	stability,increase
R1673	T5947	T5946	cc	and,stability
R1674	T5948	T5946	conj	expression,stability
R1675	T5949	T5950	punct	[,27
R1676	T5950	T5944	parataxis	27,increase
R1677	T5951	T5950	nummod	26,27
R1678	T5952	T5950	punct	",",27
R1679	T5953	T5950	punct	],27
R1680	T5954	T5936	punct	", ",intron
R1681	T5955	T5956	det	a,sequence
R1682	T5956	T5936	conj	sequence,intron
R1683	T5957	T5956	compound	Kozak,sequence
R1684	T5958	T5956	compound	consensus,sequence
R1685	T5959	T5956	prep	at,sequence
R1686	T5960	T5961	det	the,codon
R1687	T5961	T5959	pobj	codon,at
R1688	T5962	T5961	compound	initiation,codon
R1689	T5963	T5964	aux	to,optimize
R1690	T5964	T5956	advcl	optimize,sequence
R1691	T5965	T5964	dobj	translation,optimize
R1692	T5966	T5967	punct	[,28
R1693	T5967	T5964	parataxis	28,optimize
R1694	T5968	T5967	punct	],28
R1695	T5969	T5956	punct	", ",sequence
R1696	T5970	T5971	det	the,cDNA
R1697	T5971	T5956	conj	cDNA,sequence
R1698	T5972	T5971	amod	human,cDNA
R1699	T5973	T5971	compound	E2,cDNA
R1700	T5974	T5975	dep	which,modified
R1701	T5975	T5971	relcl	modified,cDNA
R1702	T5976	T5975	aux	has,modified
R1703	T5977	T5975	auxpass	been,modified
R1704	T5978	T5979	aux	to,contain
R1705	T5979	T5975	advcl	contain,modified
R1706	T5980	T5981	det	a,linker
R1707	T5981	T5979	dobj	linker,contain
R1708	T5982	T5981	nummod	4,linker
R1709	T5983	T5982	punct	×,4
R1710	T5984	T5981	compound	alanine,linker
R1711	T5985	T5981	acl	followed,linker
R1712	T5986	T5985	agent	by,followed
R1713	T5987	T5988	det	a,tag
R1714	T5988	T5986	pobj	tag,by
R1715	T5989	T5990	compound	c,myc
R1716	T5990	T5988	compound	myc,tag
R1717	T5991	T5990	punct	-,myc
R1718	T5992	T5988	compound	epitope,tag
R1719	T5993	T5988	prep	at,tag
R1720	T5994	T5995	det	the,terminus
R1721	T5995	T5993	pobj	terminus,at
R1722	T5996	T5995	compound	carboxy,terminus
R1723	T5997	T5998	aux	to,facilitate
R1724	T5998	T5988	advcl	facilitate,tag
R1725	T5999	T5998	dobj	detection,facilitate
R1726	T6000	T5971	punct	", ",cDNA
R1727	T6001	T5971	cc	and,cDNA
R1728	T6002	T6003	det	an,sequence
R1729	T6003	T5971	conj	sequence,cDNA
R1730	T6004	T6003	nmod	SV40,sequence
R1731	T6005	T6003	amod	late,sequence
R1732	T6006	T6003	compound	polyadenylation,sequence
R1733	T6007	T6003	prep	from,sequence
R1734	T6008	T6007	pobj	pCI,from
R1735	T6009	T6003	prep	for,sequence
R1736	T6010	T6011	amod	enhanced,stability
R1737	T6011	T6009	pobj	stability,for
R1738	T6012	T6011	compound	mRNA,stability
R1739	T6013	T6011	cc	and,stability
R1740	T6014	T6011	conj	translation,stability
R1741	T6015	T5895	punct	.,contains
R1742	T6017	T6018	det	The,transgene
R1743	T6018	T6024	nsubj	transgene,purified
R1744	T6019	T6020	nummod	2.48,kb
R1745	T6020	T6018	compound	kb,transgene
R1746	T6021	T6022	compound	TRE,E2
R1747	T6022	T6018	compound	E2,transgene
R1748	T6023	T6022	punct	-,E2
R1749	T6025	T6024	aux	was,purified
R1750	T6026	T6024	prep	from,purified
R1751	T6027	T6028	compound	vector,sequences
R1752	T6028	T6026	pobj	sequences,from
R1753	T6029	T6024	prep	following,purified
R1754	T6030	T6029	pobj	digestion,following
R1755	T6031	T6030	prep	with,digestion
R1756	T6032	T6031	pobj	XhoI,with
R1757	T6033	T6032	cc	and,XhoI
R1758	T6034	T6032	conj	BamHI,XhoI
R1759	T6035	T6024	cc	and,purified
R1760	T6036	T6024	conj	injected,purified
R1761	T6037	T6036	prep	into,injected
R1762	T6038	T6039	nmod	C57BL,6J
R1763	T6039	T6041	nmod	6J,Strain
R1764	T6040	T6039	punct	/,6J
R1765	T6041	T6047	compound	Strain,embryos
R1766	T6042	T6039	cc	or,6J
R1767	T6043	T6044	compound	C57BL,6J
R1768	T6044	T6039	conj	6J,6J
R1769	T6045	T6044	punct	/,6J
R1770	T6046	T6041	punct	×,Strain
R1771	T6047	T6037	pobj	embryos,into
R1772	T6048	T6047	compound	129SvEv,embryos
R1773	T6049	T6047	compound	mouse,embryos
R1774	T6050	T6024	prep	at,purified
R1775	T6051	T6052	det	the,facilities
R1776	T6052	T6050	pobj	facilities,at
R1777	T6053	T6052	amod	transgenic,facilities
R1778	T6054	T6052	compound	core,facilities
R1779	T6055	T6052	prep	of,facilities
R1780	T6056	T6057	det	the,University
R1781	T6057	T6055	pobj	University,of
R1782	T6058	T6057	prep	of,University
R1783	T6059	T6058	pobj	Pittsburgh,of
R1784	T6060	T6057	cc	and,University
R1785	T6061	T6062	det	the,University
R1786	T6062	T6057	conj	University,University
R1787	T6063	T6062	prep	of,University
R1788	T6064	T6063	pobj	Cincinnati,of
R1789	T6065	T6024	punct	", ",purified
R1790	T6066	T6024	advmod	respectively,purified
R1791	T6067	T6024	punct	.,purified
R1792	T6069	T6070	amod	Genomic,DNA
R1793	T6070	T6071	nsubjpass	DNA,screened
R1794	T6072	T6070	prep	from,DNA
R1795	T6073	T6074	det	the,tail
R1796	T6074	T6072	pobj	tail,from
R1797	T6075	T6074	prep	of,tail
R1798	T6076	T6075	pobj	mice,of
R1799	T6077	T6071	auxpass	was,screened
R1800	T6078	T6071	prep	by,screened
R1801	T6079	T6080	compound	Southern,blot
R1802	T6080	T6081	compound	blot,analysis
R1803	T6081	T6078	pobj	analysis,by
R1804	T6082	T6071	prep	following,screened
R1805	T6083	T6082	pobj	digestion,following
R1806	T6084	T6083	prep	with,digestion
R1807	T6085	T6084	pobj	EcoRI,with
R1808	T6086	T6083	cc	and,digestion
R1809	T6087	T6083	conj	hybridization,digestion
R1810	T6088	T6087	prep	to,hybridization
R1811	T6089	T6090	det	an,probe
R1812	T6090	T6088	pobj	probe,to
R1813	T6091	T6092	punct	~,400
R1814	T6092	T6093	nummod	400,bp
R1815	T6093	T6090	compound	bp,probe
R1816	T6094	T6090	acl	derived,probe
R1817	T6095	T6094	prep	from,derived
R1818	T6096	T6097	det	the,portion
R1819	T6097	T6095	pobj	portion,from
R1820	T6098	T6097	compound	SV40,portion
R1821	T6099	T6097	prep	of,portion
R1822	T6100	T6101	det	the,transgene
R1823	T6101	T6099	pobj	transgene,of
R1824	T6102	T6103	compound	TRE,E2
R1825	T6103	T6101	compound	E2,transgene
R1826	T6104	T6103	punct	-,E2
R1827	T6105	T6071	punct	.,screened
R1828	T6427	T6426	prep	of,Production
R1829	T6428	T6429	amod	intermediate,model
R1830	T6429	T6427	pobj	model,of
R1831	T6430	T6429	nmod	MSUD,model
R1832	T6431	T6429	amod	murine,model
R1833	T6433	T6434	det	The,lines
R1834	T6434	T6440	nsubjpass	lines,mated
R1835	T6435	T6434	amod	various,lines
R1836	T6436	T6437	nmod	TRE,E2
R1837	T6437	T6434	nmod	E2,lines
R1838	T6438	T6437	punct	-,E2
R1839	T6439	T6434	amod	transgenic,lines
R1840	T6441	T6434	acl	produced,lines
R1841	T6442	T6440	auxpass	were,mated
R1842	T6443	T6440	advmod	independently,mated
R1843	T6444	T6440	prep	to,mated
R1844	T6445	T6444	pobj	mice,to
R1845	T6446	T6447	dep	that,were
R1846	T6447	T6445	relcl	were,mice
R1847	T6448	T6447	acomp	heterozygous,were
R1848	T6449	T6448	prep	for,heterozygous
R1849	T6450	T6451	preconj	both,knockout
R1850	T6451	T6449	pobj	knockout,for
R1851	T6452	T6451	det	the,knockout
R1852	T6453	T6451	compound	E2,knockout
R1853	T6454	T6451	cc	and,knockout
R1854	T6455	T6456	det	the,transgene
R1855	T6456	T6451	conj	transgene,knockout
R1856	T6457	T6458	compound	LAP,tTA
R1857	T6458	T6456	compound	tTA,transgene
R1858	T6459	T6458	punct	-,tTA
R1859	T6460	T6461	punct	[,background
R1860	T6461	T6440	parataxis	background,mated
R1861	T6462	T6463	nmod	Tg,Stock
R1862	T6463	T6461	dep	Stock,background
R1863	T6464	T6465	punct	(,tTALap
R1864	T6465	T6463	parataxis	tTALap,Stock
R1865	T6466	T6465	punct	),tTALap
R1866	T6467	T6468	nmod	Bjd,J
R1867	T6468	T6463	nmod	J,Stock
R1868	T6469	T6468	punct	/,J
R1869	T6470	T6463	punct	;,Stock
R1870	T6471	T6463	nummod	3272,Stock
R1871	T6472	T6461	punct	;,background
R1872	T6473	T6474	det	The,Laboratory
R1873	T6474	T6461	dep	Laboratory,background
R1874	T6475	T6474	compound	Jackson,Laboratory
R1875	T6476	T6474	punct	", ",Laboratory
R1876	T6477	T6478	compound	Bar,Harbor
R1877	T6478	T6474	npadvmod	Harbor,Laboratory
R1878	T6479	T6474	punct	", ",Laboratory
R1879	T6480	T6474	npadvmod	ME,Laboratory
R1880	T6481	T6461	punct	;,background
R1881	T6482	T6461	nmod	NMRI,background
R1882	T6483	T6482	punct	×,NMRI
R1883	T6484	T6482	appos	FVB,NMRI
R1884	T6485	T6482	punct	×,NMRI
R1885	T6486	T6487	compound	C57BL,6J
R1886	T6487	T6482	appos	6J,NMRI
R1887	T6488	T6487	punct	/,6J
R1888	T6489	T6461	punct	],background
R1889	T6490	T6440	punct	.,mated
R1890	T6492	T6493	nsubj	Interbreeding,resulted
R1891	T6494	T6492	prep	of,Interbreeding
R1892	T6495	T6494	pobj	animals,of
R1893	T6496	T6497	dep	that,were
R1894	T6497	T6495	relcl	were,animals
R1895	T6498	T6497	acomp	heterozygous,were
R1896	T6499	T6498	prep	for,heterozygous
R1897	T6500	T6501	det	both,transgenes
R1898	T6501	T6499	pobj	transgenes,for
R1899	T6502	T6501	cc	and,transgenes
R1900	T6503	T6504	det	the,knockout
R1901	T6504	T6501	conj	knockout,transgenes
R1902	T6505	T6493	prep	in,resulted
R1903	T6506	T6507	det	the,production
R1904	T6507	T6505	pobj	production,in
R1905	T6508	T6507	prep	of,production
R1906	T6509	T6508	pobj	mice,of
R1907	T6510	T6509	prep	with,mice
R1908	T6511	T6512	det	a,variety
R1909	T6512	T6510	pobj	variety,with
R1910	T6513	T6512	prep	of,variety
R1911	T6514	T6513	pobj	genotypes,of
R1912	T6515	T6509	prep	including,mice
R1913	T6516	T6517	det	some,animals
R1914	T6517	T6515	pobj	animals,including
R1915	T6518	T6519	dep	that,were
R1916	T6519	T6517	relcl	were,animals
R1917	T6520	T6519	acomp	homozygous,were
R1918	T6521	T6520	prep	for,homozygous
R1919	T6522	T6523	det	the,knockout
R1920	T6523	T6521	pobj	knockout,for
R1921	T6524	T6519	cc	and,were
R1922	T6525	T6519	conj	were,were
R1923	T6526	T6525	acomp	positive,were
R1924	T6527	T6526	prep	for,positive
R1925	T6528	T6529	det	both,transgenes
R1926	T6529	T6527	pobj	transgenes,for
R1927	T6530	T6531	punct	(,refer
R1928	T6531	T6525	parataxis	refer,were
R1929	T6532	T6531	nsubj	we,refer
R1930	T6533	T6531	prep	to,refer
R1931	T6534	T6535	det	this,genotype
R1932	T6535	T6533	pobj	genotype,to
R1933	T6536	T6531	prep	as,refer
R1934	T6537	T6538	det	the,genotype
R1935	T6538	T6536	pobj	genotype,as
R1936	T6539	T6538	punct	"""",genotype
R1937	T6540	T6538	nmod	rescue,genotype
R1938	T6541	T6538	punct	"""",genotype
R1939	T6542	T6531	punct	),refer
R1940	T6543	T6493	punct	.,resulted
R1941	T6545	T6546	mark	If,were
R1942	T6546	T6558	advcl	were,survive
R1943	T6547	T6548	poss	our,strategy
R1944	T6548	T6546	nsubj	strategy,were
R1945	T6549	T6548	prep	for,strategy
R1946	T6550	T6549	pcomp	rescuing,for
R1947	T6551	T6552	det	the,phenotype
R1948	T6552	T6550	dobj	phenotype,rescuing
R1949	T6553	T6552	amod	neonatal,phenotype
R1950	T6554	T6552	amod	lethal,phenotype
R1951	T6555	T6552	prep	of,phenotype
R1952	T6556	T6557	det	the,knockout
R1953	T6557	T6555	pobj	knockout,of
R1954	T6559	T6546	acomp	successful,were
R1955	T6560	T6558	punct	", ",survive
R1956	T6561	T6558	advmod	then,survive
R1957	T6562	T6563	det	those,animals
R1958	T6563	T6558	nsubj	animals,survive
R1959	T6564	T6563	amod	homozygous,animals
R1960	T6565	T6563	compound	knockout,animals
R1961	T6566	T6567	dep	that,had
R1962	T6567	T6563	relcl	had,animals
R1963	T6568	T6569	det	both,transgenes
R1964	T6569	T6567	dobj	transgenes,had
R1965	T6570	T6558	aux	would,survive
R1966	T6571	T6558	prep	beyond,survive
R1967	T6572	T6573	det	the,period
R1968	T6573	T6571	pobj	period,beyond
R1969	T6574	T6573	amod	neonatal,period
R1970	T6575	T6558	punct	.,survive
R1971	T6672	T6673	det	All,mice
R1972	T6673	T6674	nsubjpass	mice,genotyped
R1973	T6675	T6674	auxpass	were,genotyped
R1974	T6676	T6674	prep	by,genotyped
R1975	T6677	T6678	compound	Southern,blot
R1976	T6678	T6679	compound	blot,analysis
R1977	T6679	T6676	pobj	analysis,by
R1978	T6680	T6674	punct	.,genotyped
R1979	T6682	T6683	amod	Genomic,DNAs
R1980	T6683	T6684	nsubjpass	DNAs,digested
R1981	T6685	T6683	acl	prepared,DNAs
R1982	T6686	T6685	prep	from,prepared
R1983	T6687	T6688	compound	tail,snips
R1984	T6688	T6686	pobj	snips,from
R1985	T6689	T6684	auxpass	were,digested
R1986	T6690	T6684	prep	with,digested
R1987	T6691	T6692	det	an,enzyme
R1988	T6692	T6690	pobj	enzyme,with
R1989	T6693	T6692	amod	appropriate,enzyme
R1990	T6694	T6692	compound	restriction,enzyme
R1991	T6695	T6684	punct	", ",digested
R1992	T6696	T6697	dep	size,fractionated
R1993	T6697	T6684	conj	fractionated,digested
R1994	T6698	T6697	prep	by,fractionated
R1995	T6699	T6700	compound	agarose,gel
R1996	T6700	T6701	compound	gel,electrophoresis
R1997	T6701	T6698	pobj	electrophoresis,by
R1998	T6702	T6697	punct	", ",fractionated
R1999	T6703	T6697	conj	blotted,fractionated
R2000	T6704	T6703	prep	to,blotted
R2001	T6705	T6704	pobj	nylon,to
R2002	T6706	T6703	punct	", ",blotted
R2003	T6707	T6703	cc	and,blotted
R2004	T6708	T6703	conj	probed,blotted
R2005	T6709	T6708	advcl	using,probed
R2006	T6710	T6711	amod	standard,procedures
R2007	T6711	T6709	dobj	procedures,using
R2008	T6712	T6684	punct	.,digested
R2009	T7185	T7186	amod	Primary,fibroblasts
R2010	T7186	T7189	nsubjpass	fibroblasts,prepared
R2011	T7187	T7186	nmod	mouse,fibroblasts
R2012	T7188	T7186	amod	embryonic,fibroblasts
R2013	T7190	T7189	auxpass	were,prepared
R2014	T7191	T7189	prep	from,prepared
R2015	T7192	T7193	amod	embryonic,fetuses
R2016	T7193	T7191	pobj	fetuses,from
R2017	T7194	T7195	nmod	day,16.5
R2018	T7195	T7193	nummod	16.5,fetuses
R2019	T7196	T7195	punct	~,16.5
R2020	T7197	T7198	punct	–,18.5
R2021	T7198	T7195	prep	18.5,16.5
R2022	T7199	T7200	mark	as,described
R2023	T7200	T7189	advcl	described,prepared
R2024	T7201	T7202	punct	[,29
R2025	T7202	T7189	parataxis	29,prepared
R2026	T7203	T7202	punct	],29
R2027	T7204	T7189	punct	.,prepared
R2028	T7206	T7207	nsubjpass	Fibroblasts,passed
R2029	T7208	T7207	auxpass	were,passed
R2030	T7209	T7207	prep	onto,passed
R2031	T7210	T7209	pobj	glass,onto
R2032	T7211	T7207	punct	", ",passed
R2033	T7212	T7207	conj	fixed,passed
R2034	T7213	T7212	prep	in,fixed
R2035	T7214	T7215	nummod	2,%
R2036	T7215	T7216	compound	%,paraformaldehyde
R2037	T7216	T7213	pobj	paraformaldehyde,in
R2038	T7217	T7212	prep	in,fixed
R2039	T7218	T7217	pobj	PBS,in
R2040	T7219	T7212	prep	for,fixed
R2041	T7220	T7221	nummod	10,minutes
R2042	T7221	T7219	pobj	minutes,for
R2043	T7222	T7212	punct	", ",fixed
R2044	T7223	T7212	conj	permeabilized,fixed
R2045	T7224	T7223	prep	in,permeabilized
R2046	T7225	T7226	nummod	2,%
R2047	T7226	T7227	compound	%,paraformaldehyde
R2048	T7227	T7224	pobj	paraformaldehyde,in
R2049	T7228	T7227	acl	containing,paraformaldehyde
R2050	T7229	T7230	nummod	0.1,%
R2051	T7230	T7231	compound	%,X100
R2052	T7231	T7228	dobj	X100,containing
R2053	T7232	T7231	compound	Triton,X100
R2054	T7233	T7223	prep	for,permeabilized
R2055	T7234	T7235	nummod	10,minutes
R2056	T7235	T7233	pobj	minutes,for
R2057	T7236	T7223	cc	and,permeabilized
R2058	T7237	T7223	conj	washed,permeabilized
R2059	T7238	T7239	nummod	three,times
R2060	T7239	T7237	npadvmod	times,washed
R2061	T7240	T7237	prep	in,washed
R2062	T7241	T7240	pobj	PBS,in
R2063	T7242	T7241	acl	containing,PBS
R2064	T7243	T7244	nummod	0.5,%
R2065	T7244	T7245	compound	%,BSA
R2066	T7245	T7242	dobj	BSA,containing
R2067	T7246	T7245	cc	and,BSA
R2068	T7247	T7248	nummod	0.15,%
R2069	T7248	T7249	compound	%,glycine
R2070	T7249	T7245	conj	glycine,BSA
R2071	T7250	T7242	punct	", ",containing
R2072	T7251	T7242	npadvmod	pH,containing
R2073	T7252	T7251	nummod	7.4,pH
R2074	T7253	T7254	punct	(,A
R2075	T7254	T7242	parataxis	A,containing
R2076	T7255	T7254	compound	Buffer,A
R2077	T7256	T7254	punct	),A
R2078	T7257	T7207	punct	.,passed
R2079	T7259	T7260	prep	Following,incubated
R2080	T7261	T7262	det	a,incubation
R2081	T7262	T7259	pobj	incubation,Following
R2082	T7263	T7264	nummod	30,min
R2083	T7264	T7262	compound	min,incubation
R2084	T7265	T7262	prep	with,incubation
R2085	T7266	T7267	amod	purified,IgG
R2086	T7267	T7265	pobj	IgG,with
R2087	T7268	T7267	compound	goat,IgG
R2088	T7269	T7270	punct	(,μg
R2089	T7270	T7267	parataxis	μg,IgG
R2090	T7271	T7270	nummod	50,μg
R2091	T7272	T7270	punct	(,μg
R2092	T7273	T7274	punct	/,ml
R2093	T7274	T7270	prep	ml,μg
R2094	T7275	T7270	punct	),μg
R2095	T7276	T7262	prep	at,incubation
R2096	T7277	T7278	nummod	25,°C
R2097	T7278	T7276	pobj	°C,at
R2098	T7279	T7262	cc	and,incubation
R2099	T7280	T7281	nummod	three,washes
R2100	T7281	T7262	conj	washes,incubation
R2101	T7282	T7281	amod	additional,washes
R2102	T7283	T7281	prep	with,washes
R2103	T7284	T7285	compound	Buffer,A
R2104	T7285	T7283	pobj	A,with
R2105	T7286	T7260	punct	", ",incubated
R2106	T7287	T7260	nsubjpass	cells,incubated
R2107	T7288	T7260	auxpass	were,incubated
R2108	T7289	T7260	prep	for,incubated
R2109	T7290	T7291	nummod	60,min
R2110	T7291	T7289	pobj	min,for
R2111	T7292	T7260	prep	with,incubated
R2112	T7293	T7294	npadvmod	E2,specific
R2113	T7294	T7296	amod	specific,antiserum
R2114	T7295	T7294	punct	-,specific
R2115	T7296	T7292	pobj	antiserum,with
R2116	T7297	T7298	punct	[,30
R2117	T7298	T7296	parataxis	30,antiserum
R2118	T7299	T7298	punct	],30
R2119	T7300	T7296	prep	at,antiserum
R2120	T7301	T7302	nummod	1,μg
R2121	T7302	T7300	pobj	μg,at
R2122	T7303	T7304	punct	/,ml
R2123	T7304	T7302	prep	ml,μg
R2124	T7305	T7260	advcl	followed,incubated
R2125	T7306	T7305	agent	by,followed
R2126	T7307	T7308	nummod	three,washes
R2127	T7308	T7306	pobj	washes,by
R2128	T7309	T7308	prep	in,washes
R2129	T7310	T7311	compound	Buffer,A
R2130	T7311	T7309	pobj	A,in
R2131	T7312	T7308	cc	and,washes
R2132	T7313	T7314	nummod	60,minute
R2133	T7314	T7315	compound	minute,incubation
R2134	T7315	T7308	conj	incubation,washes
R2135	T7316	T7315	prep	in,incubation
R2136	T7317	T7318	advmod	fluorescently,labeled
R2137	T7318	T7319	amod	labeled,antibody
R2138	T7319	T7316	pobj	antibody,in
R2139	T7320	T7319	amod	second,antibody
R2140	T7321	T7322	punct	(,μg
R2141	T7322	T7260	parataxis	μg,incubated
R2142	T7323	T7324	quantmod	1,2
R2143	T7324	T7322	nummod	2,μg
R2144	T7325	T7324	punct	–,2
R2145	T7326	T7327	punct	/,ml
R2146	T7327	T7322	prep	ml,μg
R2147	T7328	T7322	punct	),μg
R2148	T7329	T7260	punct	.,incubated
R2149	T7331	T7332	det	The,cells
R2150	T7332	T7333	nsubjpass	cells,washed
R2151	T7334	T7333	auxpass	were,washed
R2152	T7335	T7333	advmod	then,washed
R2153	T7336	T7337	nummod	six,times
R2154	T7337	T7333	npadvmod	times,washed
R2155	T7338	T7339	punct	(,min
R2156	T7339	T7337	parataxis	min,times
R2157	T7340	T7339	nummod	5,min
R2158	T7341	T7342	punct	/,wash
R2159	T7342	T7339	prep	wash,min
R2160	T7343	T7339	punct	),min
R2161	T7344	T7333	prep	in,washed
R2162	T7345	T7346	compound	Buffer,A
R2163	T7346	T7344	pobj	A,in
R2164	T7347	T7333	cc	and,washed
R2165	T7348	T7349	advmod	then,mounted
R2166	T7349	T7333	conj	mounted,washed
R2167	T7350	T7349	prep	in,mounted
R2168	T7351	T7350	pobj	gelvatol,in
R2169	T7352	T7353	punct	(,Monsanto
R2170	T7353	T7351	parataxis	Monsanto,gelvatol
R2171	T7354	T7353	punct	", ",Monsanto
R2172	T7355	T7356	compound	St,Louis
R2173	T7356	T7353	npadvmod	Louis,Monsanto
R2174	T7357	T7353	punct	),Monsanto
R2175	T7358	T7333	punct	.,washed
R2176	T7360	T7361	advmod	When,examined
R2177	T7361	T7367	advcl	examined,was
R2178	T7362	T7361	nsubjpass	livers,examined
R2179	T7363	T7362	prep	from,livers
R2180	T7364	T7365	amod	newborn,pups
R2181	T7365	T7363	pobj	pups,from
R2182	T7366	T7361	auxpass	were,examined
R2183	T7368	T7367	punct	", ",was
R2184	T7369	T7367	nsubj	fixation,was
R2185	T7370	T7367	prep	by,was
R2186	T7371	T7370	pobj	immersion,by
R2187	T7372	T7371	prep	in,immersion
R2188	T7373	T7374	nummod	2,%
R2189	T7374	T7375	compound	%,paraformaldehyde
R2190	T7375	T7372	pobj	paraformaldehyde,in
R2191	T7376	T7371	acl	followed,immersion
R2192	T7377	T7376	agent	by,followed
R2193	T7378	T7377	pobj	cryoprotection,by
R2194	T7379	T7378	cc	and,cryoprotection
R2195	T7380	T7381	compound	shock,freezing
R2196	T7381	T7378	conj	freezing,cryoprotection
R2197	T7382	T7378	prep	in,cryoprotection
R2198	T7383	T7384	amod	liquid,nitrogen
R2199	T7384	T7385	npadvmod	nitrogen,cooled
R2200	T7385	T7386	amod	cooled,isopentane
R2201	T7386	T7382	pobj	isopentane,in
R2202	T7387	T7378	cc	and,cryoprotection
R2203	T7388	T7378	conj	sectioning,cryoprotection
R2204	T7389	T7390	punct	(,microns
R2205	T7390	T7388	parataxis	microns,sectioning
R2206	T7391	T7390	nummod	5,microns
R2207	T7392	T7390	punct	),microns
R2208	T7393	T7367	punct	.,was
R2209	T7395	T7396	advmod	Otherwise,was
R2210	T7397	T7396	nsubj	processing,was
R2211	T7398	T7396	prep	as,was
R2212	T7399	T7398	prep	for,as
R2213	T7400	T7401	det	the,cells
R2214	T7401	T7399	pobj	cells,for
R2215	T7402	T7401	advmod	above,cells
R2216	T7403	T7396	punct	(,was
R2217	T7404	T7396	prep	without,was
R2218	T7405	T7406	det	the,steps
R2219	T7406	T7404	pobj	steps,without
R2220	T7407	T7406	nmod	fixation,steps
R2221	T7408	T7407	cc	and,fixation
R2222	T7409	T7407	conj	permabilization,fixation
R2223	T7410	T7396	punct	),was
R2224	T7411	T7396	punct	.,was
R2225	T7545	T7546	compound	Amino,acid
R2226	T7546	T7547	compound	acid,analysis
R2227	T7549	T7550	nsubjpass	Blood,collected
R2228	T7551	T7550	auxpass	was,collected
R2229	T7552	T7550	prep	from,collected
R2230	T7553	T7554	det	the,vein
R2231	T7554	T7552	pobj	vein,from
R2232	T7555	T7554	amod	retroorbital,vein
R2233	T7556	T7554	nmod	sinus,vein
R2234	T7557	T7556	cc	or,sinus
R2235	T7558	T7556	conj	tail,sinus
R2236	T7559	T7554	prep	of,vein
R2237	T7560	T7559	pobj	mice,of
R2238	T7561	T7550	cc	and,collected
R2239	T7562	T7550	conj	spotted,collected
R2240	T7563	T7562	prep	on,spotted
R2241	T7564	T7565	det	a,paper
R2242	T7565	T7563	pobj	paper,on
R2243	T7566	T7565	compound	filter,paper
R2244	T7567	T7568	advmod	routinely,used
R2245	T7568	T7565	acl	used,paper
R2246	T7569	T7568	prep	for,used
R2247	T7570	T7571	compound	blood,analysis
R2248	T7571	T7569	pobj	analysis,for
R2249	T7572	T7573	compound	amino,acid
R2250	T7573	T7571	compound	acid,analysis
R2251	T7574	T7571	prep	for,analysis
R2252	T7575	T7576	amod	prenatal,screening
R2253	T7576	T7574	pobj	screening,for
R2254	T7577	T7550	punct	.,collected
R2255	T7579	T7580	nsubjpass	Concentrations,determined
R2256	T7581	T7579	prep	of,Concentrations
R2257	T7582	T7581	pobj	BCAA,of
R2258	T7583	T7582	cc	and,BCAA
R2259	T7584	T7585	amod	other,acids
R2260	T7585	T7582	conj	acids,BCAA
R2261	T7586	T7585	compound	amino,acids
R2262	T7587	T7579	prep	in,Concentrations
R2263	T7588	T7587	pobj	blood,in
R2264	T7589	T7580	auxpass	were,determined
R2265	T7590	T7580	prep	by,determined
R2266	T7591	T7592	amod	tandem,spectrometry
R2267	T7592	T7590	pobj	spectrometry,by
R2268	T7593	T7592	compound	mass,spectrometry
R2269	T7594	T7595	punct	(,Screening
R2270	T7595	T7592	parataxis	Screening,spectrometry
R2271	T7596	T7595	compound	Pediatrix,Screening
R2272	T7597	T7595	punct	", ",Screening
R2273	T7598	T7595	npadvmod	Bridgeville,Screening
R2274	T7599	T7595	punct	", ",Screening
R2275	T7600	T7595	npadvmod	PA,Screening
R2276	T7601	T7595	punct	),Screening
R2277	T7602	T7580	punct	.,determined
R2282	T8106	T8105	prep	of,Assay
R2283	T8107	T8108	compound	BCKDH,activity
R2284	T8108	T8106	pobj	activity,of
R2285	T8110	T8111	nsubjpass	Livers,removed
R2286	T8112	T8111	auxpass	were,removed
R2287	T8113	T8111	punct	", ",removed
R2288	T8114	T8111	conj	frozen,removed
R2289	T8115	T8114	prep	in,frozen
R2290	T8116	T8117	amod	liquid,nitrogen
R2291	T8117	T8115	pobj	nitrogen,in
R2292	T8118	T8114	punct	", ",frozen
R2293	T8119	T8114	cc	and,frozen
R2294	T8120	T8114	conj	stored,frozen
R2295	T8121	T8120	prep	at,stored
R2296	T8122	T8123	punct	-,80
R2297	T8123	T8124	nummod	80,°C
R2298	T8124	T8121	pobj	°C,at
R2299	T8125	T8111	punct	.,removed
R2300	T8127	T8128	prep	At,thawed
R2301	T8129	T8130	det	the,time
R2302	T8130	T8127	pobj	time,At
R2303	T8131	T8130	prep	of,time
R2304	T8132	T8133	compound	enzyme,assay
R2305	T8133	T8131	pobj	assay,of
R2306	T8134	T8128	punct	", ",thawed
R2307	T8135	T8128	nsubjpass	livers,thawed
R2308	T8136	T8128	auxpass	were,thawed
R2309	T8137	T8128	punct	", ",thawed
R2310	T8138	T8128	cc	and,thawed
R2311	T8139	T8128	conj	homogenized,thawed
R2312	T8140	T8141	punct	(,v
R2313	T8141	T8139	parataxis	v,homogenized
R2314	T8142	T8143	nummod	1,9
R2315	T8143	T8141	dep	9,v
R2316	T8144	T8143	punct	:,9
R2317	T8145	T8141	punct	", ",v
R2318	T8146	T8141	compound	w,v
R2319	T8147	T8141	punct	/,v
R2320	T8148	T8141	punct	),v
R2321	T8149	T8139	prep	in,homogenized
R2322	T8150	T8151	nummod	0.25,M
R2323	T8151	T8152	compound	M,sucrose
R2324	T8152	T8149	pobj	sucrose,in
R2325	T8153	T8152	punct	", ",sucrose
R2326	T8154	T8155	nummod	10,mM
R2327	T8155	T8156	compound	mM,HC1
R2328	T8156	T8152	appos	HC1,sucrose
R2329	T8157	T8156	compound	Tris,HC1
R2330	T8158	T8156	punct	-,HC1
R2331	T8159	T8156	punct	", ",HC1
R2332	T8160	T8156	npadvmod	pH,HC1
R2333	T8161	T8160	nummod	7.4,pH
R2334	T8162	T8128	punct	.,thawed
R2335	T8164	T8165	compound	Liver,homogenates
R2336	T8165	T8166	nsubjpass	homogenates,centrifuged
R2337	T8167	T8166	auxpass	were,centrifuged
R2338	T8168	T8166	prep	at,centrifuged
R2339	T8169	T8170	nummod	600,g
R2340	T8170	T8168	pobj	g,at
R2341	T8171	T8169	punct	×,600
R2342	T8172	T8166	prep	for,centrifuged
R2343	T8173	T8174	nummod	10,min
R2344	T8174	T8172	pobj	min,for
R2345	T8175	T8166	prep	at,centrifuged
R2346	T8176	T8177	nummod	4,°C
R2347	T8177	T8175	pobj	°C,at
R2348	T8178	T8166	cc	and,centrifuged
R2349	T8179	T8180	det	the,fraction
R2350	T8180	T8182	nsubjpass	fraction,saved
R2351	T8181	T8180	compound	supernatant,fraction
R2352	T8182	T8166	conj	saved,centrifuged
R2353	T8183	T8182	auxpass	was,saved
R2354	T8184	T8185	aux	to,determine
R2355	T8185	T8182	advcl	determine,saved
R2356	T8186	T8187	det	the,activity
R2357	T8187	T8185	dobj	activity,determine
R2358	T8188	T8187	compound	BCKDH,activity
R2359	T8189	T8182	punct	.,saved
R2360	T8191	T8192	det	The,use
R2361	T8192	T8193	nsubjpass	use,necessitated
R2362	T8194	T8192	prep	of,use
R2363	T8195	T8196	compound	tissue,homogenates
R2364	T8196	T8194	pobj	homogenates,of
R2365	T8197	T8193	auxpass	was,necessitated
R2366	T8198	T8193	agent	by,necessitated
R2367	T8199	T8200	det	the,availability
R2368	T8200	T8198	pobj	availability,by
R2369	T8201	T8200	amod	limited,availability
R2370	T8202	T8200	prep	of,availability
R2371	T8203	T8204	compound	liver,tissue
R2372	T8204	T8202	pobj	tissue,of
R2373	T8205	T8204	punct	", ",tissue
R2374	T8206	T8207	advmod	particularly,from
R2375	T8207	T8204	prep	from,tissue
R2376	T8208	T8209	amod	newborn,pups
R2377	T8209	T8207	pobj	pups,from
R2378	T8210	T8193	punct	.,necessitated
R2379	T8212	T8213	compound	BCKDH,activity
R2380	T8213	T8214	nsubjpass	activity,determined
R2381	T8215	T8214	auxpass	was,determined
R2382	T8216	T8214	prep	by,determined
R2383	T8217	T8216	pcomp	measuring,by
R2384	T8218	T8219	det	the,release
R2385	T8219	T8217	dobj	release,measuring
R2386	T8220	T8219	prep	of,release
R2387	T8221	T8220	pobj	14CO2,of
R2388	T8222	T8217	prep	from,measuring
R2389	T8223	T8224	nmod	α,keto
R2390	T8224	T8226	nmod	keto,isocaproate
R2391	T8225	T8224	punct	-,keto
R2392	T8226	T8222	pobj	isocaproate,from
R2393	T8227	T8228	punct	[,1
R2394	T8228	T8224	parataxis	1,keto
R2395	T8229	T8230	punct	-,14C
R2396	T8230	T8228	prep	14C,1
R2397	T8231	T8228	punct	],1
R2398	T8232	T8233	mark	as,described
R2399	T8233	T8214	advcl	described,determined
R2400	T8234	T8233	advmod	previously,described
R2401	T8235	T8236	punct	[,31
R2402	T8236	T8233	parataxis	31,described
R2403	T8237	T8236	punct	],31
R2404	T8238	T8214	punct	.,determined
R2405	T8240	T8241	det	The,mixture
R2406	T8241	T8244	nsubj	mixture,contained
R2407	T8242	T8241	amod	complete,mixture
R2408	T8243	T8241	compound	reaction,mixture
R2409	T8245	T8246	punct	(,volume
R2410	T8246	T8244	parataxis	volume,contained
R2411	T8247	T8246	amod	final,volume
R2412	T8248	T8249	nummod	1,ml
R2413	T8249	T8246	appos	ml,volume
R2414	T8250	T8246	punct	),volume
R2415	T8251	T8252	nummod	30,mM
R2416	T8252	T8253	compound	mM,buffer
R2417	T8253	T8244	dobj	buffer,contained
R2418	T8254	T8255	compound	potassium,phosphate
R2419	T8255	T8253	compound	phosphate,buffer
R2420	T8256	T8253	punct	", ",buffer
R2421	T8257	T8253	npadvmod	pH,buffer
R2422	T8258	T8257	nummod	7.4,pH
R2423	T8259	T8253	punct	", ",buffer
R2424	T8260	T8261	nummod	0.20,mM
R2425	T8261	T8262	compound	mM,ketoisocaproate
R2426	T8262	T8253	conj	ketoisocaproate,buffer
R2427	T8263	T8262	compound	α,ketoisocaproate
R2428	T8264	T8262	punct	-,ketoisocaproate
R2429	T8265	T8262	punct	", ",ketoisocaproate
R2430	T8266	T8267	nummod	0.40,mM
R2431	T8267	T8268	compound	mM,CoASH
R2432	T8268	T8262	conj	CoASH,ketoisocaproate
R2433	T8269	T8268	punct	", ",CoASH
R2434	T8270	T8271	nummod	0.40,mM
R2435	T8271	T8272	compound	mM,pyrophosphate
R2436	T8272	T8268	conj	pyrophosphate,CoASH
R2437	T8273	T8272	compound	thiamin,pyrophosphate
R2438	T8274	T8272	punct	", ",pyrophosphate
R2439	T8275	T8276	nummod	2,mM
R2440	T8276	T8277	compound	mM,NAD
R2441	T8277	T8272	conj	NAD,pyrophosphate
R2442	T8278	T8277	punct	+,NAD
R2443	T8279	T8277	punct	", ",NAD
R2444	T8280	T8281	nummod	2,mM
R2445	T8281	T8282	compound	mM,dithiothreitol
R2446	T8282	T8277	conj	dithiothreitol,NAD
R2447	T8283	T8282	punct	", ",dithiothreitol
R2448	T8284	T8285	nummod	5,mM
R2449	T8285	T8286	compound	mM,Mg2
R2450	T8286	T8282	conj	Mg2,dithiothreitol
R2451	T8287	T8286	punct	+,Mg2
R2452	T8288	T8286	punct	", ",Mg2
R2453	T8289	T8290	advmod	approximately,"250,000"
R2454	T8290	T8291	nummod	"250,000",DPM
R2455	T8291	T8286	conj	DPM,Mg2
R2456	T8292	T8291	prep	of,DPM
R2457	T8293	T8294	nmod	α,keto
R2458	T8294	T8296	nmod	keto,isocaproate
R2459	T8295	T8294	punct	-,keto
R2460	T8296	T8292	pobj	isocaproate,of
R2461	T8297	T8298	punct	[,1
R2462	T8298	T8294	parataxis	1,keto
R2463	T8299	T8300	punct	-,14C
R2464	T8300	T8298	prep	14C,1
R2465	T8301	T8298	punct	],1
R2466	T8302	T8291	punct	", ",DPM
R2467	T8303	T8291	cc	and,DPM
R2468	T8304	T8305	nummod	0.10,ml
R2469	T8305	T8291	conj	ml,DPM
R2470	T8306	T8305	prep	of,ml
R2471	T8307	T8308	compound	liver,homogenate
R2472	T8308	T8306	pobj	homogenate,of
R2473	T8309	T8310	punct	(,protein
R2474	T8310	T8308	parataxis	protein,homogenate
R2475	T8311	T8312	quantmod	2,3
R2476	T8312	T8314	nummod	3,mg
R2477	T8313	T8312	punct	–,3
R2478	T8314	T8310	compound	mg,protein
R2479	T8315	T8310	punct	),protein
R2480	T8316	T8244	punct	.,contained
R2481	T8318	T8319	nsubjpass	Assays,carried
R2482	T8320	T8319	auxpass	were,carried
R2483	T8321	T8319	prt	out,carried
R2484	T8322	T8319	prep	for,carried
R2485	T8323	T8324	nummod	15,min
R2486	T8324	T8322	pobj	min,for
R2487	T8325	T8319	prep	at,carried
R2488	T8326	T8327	nummod	37,°C
R2489	T8327	T8325	pobj	°C,at
R2490	T8328	T8319	punct	", ",carried
R2491	T8329	T8330	nsubjpass	14CO2,trapped
R2492	T8330	T8319	conj	trapped,carried
R2493	T8331	T8330	auxpass	was,trapped
R2494	T8332	T8330	prep	in,trapped
R2495	T8333	T8332	pobj	hydroxide,in
R2496	T8334	T8333	prep	of,hydroxide
R2497	T8335	T8334	pobj	Hyamine,of
R2498	T8336	T8330	punct	", ",trapped
R2499	T8337	T8330	cc	and,trapped
R2500	T8338	T8339	nsubjpass	radioactivity,determined
R2501	T8339	T8330	conj	determined,trapped
R2502	T8340	T8339	auxpass	was,determined
R2503	T8341	T8339	prep	by,determined
R2504	T8342	T8343	amod	liquid,scintillation
R2505	T8343	T8344	compound	scintillation,spectrometry
R2506	T8344	T8341	pobj	spectrometry,by
R2507	T8345	T8339	punct	.,determined
R2508	T8817	T8818	compound	Western,blot
R2509	T8818	T8819	compound	blot,analysis
R2510	T8821	T8822	compound	Protein,extracts
R2511	T8822	T8823	nsubjpass	extracts,isolated
R2512	T8824	T8823	auxpass	were,isolated
R2513	T8825	T8823	prep	from,isolated
R2514	T8826	T8827	amod	homogenized,liver
R2515	T8827	T8825	pobj	liver,from
R2516	T8828	T8827	punct	(,liver
R2517	T8829	T8830	advmod	freshly,harvested
R2518	T8830	T8827	acl	harvested,liver
R2519	T8831	T8830	cc	and,harvested
R2520	T8832	T8833	dep	flash,frozen
R2521	T8833	T8830	conj	frozen,harvested
R2522	T8834	T8827	punct	),liver
R2523	T8835	T8827	prep	of,liver
R2524	T8836	T8837	npadvmod	wildtype,transgenic
R2525	T8837	T8845	amod	transgenic,mice
R2526	T8838	T8836	punct	", ",wildtype
R2527	T8839	T8840	compound	Line,525A
R2528	T8840	T8836	conj	525A,wildtype
R2529	T8841	T8840	punct	", ",525A
R2530	T8842	T8840	cc	and,525A
R2531	T8843	T8844	compound	Line,A
R2532	T8844	T8840	conj	A,525A
R2533	T8845	T8835	pobj	mice,of
R2534	T8846	T8823	punct	.,isolated
R2535	T8848	T8849	nsubjpass	Protein,analyzed
R2536	T8850	T8851	punct	(,μg
R2537	T8851	T8848	parataxis	μg,Protein
R2538	T8852	T8851	nummod	25,μg
R2539	T8853	T8851	prep	per,μg
R2540	T8854	T8853	pobj	sample,per
R2541	T8855	T8851	punct	),μg
R2542	T8856	T8849	auxpass	was,analyzed
R2543	T8857	T8849	prep	by,analyzed
R2544	T8858	T8857	pobj	electrophoresis,by
R2545	T8859	T8849	prep	on,analyzed
R2546	T8860	T8861	det	a,Gel
R2547	T8861	T8859	pobj	Gel,on
R2548	T8862	T8863	nummod	10,%
R2549	T8863	T8861	nmod	%,Gel
R2550	T8864	T8865	nmod	SDS,PAGE
R2551	T8865	T8861	nmod	PAGE,Gel
R2552	T8866	T8865	punct	-,PAGE
R2553	T8867	T8861	amod	Ready,Gel
R2554	T8868	T8869	punct	(,Rad
R2555	T8869	T8861	parataxis	Rad,Gel
R2556	T8870	T8869	compound	Bio,Rad
R2557	T8871	T8869	punct	-,Rad
R2558	T8872	T8869	punct	", ",Rad
R2559	T8873	T8869	npadvmod	Hercules,Rad
R2560	T8874	T8869	punct	", ",Rad
R2561	T8875	T8869	npadvmod	CA,Rad
R2562	T8876	T8869	punct	),Rad
R2563	T8877	T8849	cc	and,analyzed
R2564	T8878	T8849	conj	transferred,analyzed
R2565	T8879	T8878	prep	to,transferred
R2566	T8880	T8881	compound	PVDF,membrane
R2567	T8881	T8879	pobj	membrane,to
R2568	T8882	T8883	punct	(,Rad
R2569	T8883	T8881	parataxis	Rad,membrane
R2570	T8884	T8885	compound	Sequi,Blot
R2571	T8885	T8883	dep	Blot,Rad
R2572	T8886	T8885	punct	-,Blot
R2573	T8887	T8883	punct	;,Rad
R2574	T8888	T8883	compound	Bio,Rad
R2575	T8889	T8883	punct	-,Rad
R2576	T8890	T8883	punct	),Rad
R2577	T8891	T8878	prep	via,transferred
R2578	T8892	T8891	pobj	electroblotting,via
R2579	T8893	T8849	punct	.,analyzed
R2580	T8895	T8896	det	All,blots
R2581	T8896	T8897	nsubjpass	blots,probed
R2582	T8898	T8897	auxpass	were,probed
R2583	T8899	T8897	prep	for,probed
R2584	T8900	T8901	compound	E2,protein
R2585	T8901	T8899	pobj	protein,for
R2586	T8902	T8897	advcl	using,probed
R2587	T8903	T8904	amod	polyclonal,antisera
R2588	T8904	T8902	dobj	antisera,using
R2589	T8905	T8904	compound	rabbit,antisera
R2590	T8906	T8904	compound	E2,antisera
R2591	T8907	T8908	punct	(,"5,000"
R2592	T8908	T8904	parataxis	"5,000",antisera
R2593	T8909	T8908	nummod	1,"5,000"
R2594	T8910	T8908	punct	:,"5,000"
R2595	T8911	T8908	punct	),"5,000"
R2596	T8912	T8904	punct	", ",antisera
R2597	T8913	T8914	dep	which,detects
R2598	T8914	T8904	relcl	detects,antisera
R2599	T8915	T8916	preconj	both,subunits
R2600	T8916	T8914	dobj	subunits,detects
R2601	T8917	T8916	nmod	mouse,subunits
R2602	T8918	T8919	punct	(,kD
R2603	T8919	T8917	parataxis	kD,mouse
R2604	T8920	T8921	punct	~,47
R2605	T8921	T8919	nummod	47,kD
R2606	T8922	T8919	punct	),kD
R2607	T8923	T8917	cc	and,mouse
R2608	T8924	T8917	conj	human,mouse
R2609	T8925	T8926	punct	(,kD
R2610	T8926	T8924	parataxis	kD,human
R2611	T8927	T8928	punct	~,54
R2612	T8928	T8926	nummod	54,kD
R2613	T8929	T8926	punct	),kD
R2614	T8930	T8916	compound	E2,subunits
R2615	T8931	T8932	punct	(,gift
R2616	T8932	T8916	parataxis	gift,subunits
R2617	T8933	T8932	punct	[,gift
R2618	T8934	T8932	dep	30,gift
R2619	T8935	T8932	punct	],gift
R2620	T8936	T8932	punct	;,gift
R2621	T8937	T8932	prep	from,gift
R2622	T8938	T8939	compound	Dr.,Hutson
R2623	T8939	T8937	pobj	Hutson,from
R2624	T8940	T8939	compound	Susan,Hutson
R2625	T8941	T8939	punct	", ",Hutson
R2626	T8942	T8943	compound	Wake,Forest
R2627	T8943	T8944	compound	Forest,University
R2628	T8944	T8939	npadvmod	University,Hutson
R2629	T8945	T8932	punct	),gift
R2630	T8946	T8897	punct	.,probed
R2631	T8948	T8949	nsubjpass	Blots,re-probed
R2632	T8950	T8949	auxpass	were,re-probed
R2633	T8951	T8949	prep	with,re-probed
R2634	T8952	T8953	det	a,antibody
R2635	T8953	T8951	pobj	antibody,with
R2636	T8954	T8953	nmod	rabbit,antibody
R2637	T8955	T8956	amod	anti-c,myc
R2638	T8956	T8953	compound	myc,antibody
R2639	T8957	T8956	punct	-,myc
R2640	T8958	T8953	compound	tag,antibody
R2641	T8959	T8960	punct	(,ab9106
R2642	T8960	T8953	parataxis	ab9106,antibody
R2643	T8961	T8962	nummod	1,"10,000"
R2644	T8962	T8960	dep	"10,000",ab9106
R2645	T8963	T8962	punct	:,"10,000"
R2646	T8964	T8960	punct	;,ab9106
R2647	T8965	T8960	dep	abCam,ab9106
R2648	T8966	T8965	punct	", ",abCam
R2649	T8967	T8965	npadvmod	Cambridge,abCam
R2650	T8968	T8965	punct	", ",abCam
R2651	T8969	T8965	npadvmod	MA,abCam
R2652	T8970	T8960	punct	;,ab9106
R2653	T8971	T8960	nmod	cat.,ab9106
R2654	T8972	T8960	punct	#,ab9106
R2655	T8973	T8960	punct	-,ab9106
R2656	T8974	T8960	nummod	100,ab9106
R2657	T8975	T8960	punct	),ab9106
R2658	T8976	T8949	punct	.,re-probed
R2659	T8978	T8979	nsubjpass	Blots,re-probed
R2660	T8980	T8979	auxpass	were,re-probed
R2661	T8981	T8979	advmod	also,re-probed
R2662	T8982	T8979	prep	with,re-probed
R2663	T8983	T8984	det	an,antibody
R2664	T8984	T8982	pobj	antibody,with
R2665	T8985	T8984	prep	for,antibody
R2666	T8986	T8987	compound	β,actin
R2667	T8987	T8985	pobj	actin,for
R2668	T8988	T8987	punct	-,actin
R2669	T8989	T8990	punct	(,ab8227
R2670	T8990	T8987	parataxis	ab8227,actin
R2671	T8991	T8992	nummod	43,kD
R2672	T8992	T8990	dep	kD,ab8227
R2673	T8993	T8990	punct	;,ab8227
R2674	T8994	T8995	nummod	1,"10,000"
R2675	T8995	T8990	dep	"10,000",ab8227
R2676	T8996	T8995	punct	:,"10,000"
R2677	T8997	T8990	punct	;,ab8227
R2678	T8998	T8990	dep	abCam,ab8227
R2679	T8999	T8990	punct	;,ab8227
R2680	T9000	T8990	nmod	cat.,ab8227
R2681	T9001	T8990	punct	#,ab8227
R2682	T9002	T8990	punct	-,ab8227
R2683	T9003	T8990	nummod	50,ab8227
R2684	T9004	T8990	punct	),ab8227
R2685	T9005	T9006	aux	to,allow
R2686	T9006	T8979	advcl	allow,re-probed
R2687	T9007	T9006	prep	for,allow
R2688	T9008	T9009	compound	loading,comparisons
R2689	T9009	T9007	pobj	comparisons,for
R2690	T9010	T8979	punct	.,re-probed
R2691	T9012	T9013	det	A,antibody
R2692	T9013	T9017	nsubjpass	antibody,used
R2693	T9014	T9013	nmod	goat,antibody
R2694	T9015	T9013	amod	anti-rabbit,antibody
R2695	T9016	T9013	amod	secondary,antibody
R2696	T9018	T9013	acl	conjugated,antibody
R2697	T9019	T9018	prep	to,conjugated
R2698	T9020	T9021	compound	horseradish,peroxidase
R2699	T9021	T9019	pobj	peroxidase,to
R2700	T9022	T9023	punct	(,H
R2701	T9023	T9021	parataxis	H,peroxidase
R2702	T9024	T9025	nummod	1,"10,000"
R2703	T9025	T9023	dep	"10,000",H
R2704	T9026	T9025	punct	:,"10,000"
R2705	T9027	T9023	punct	;,H
R2706	T9028	T9023	dep	Novus,H
R2707	T9029	T9028	punct	", ",Novus
R2708	T9030	T9028	npadvmod	Littleton,Novus
R2709	T9031	T9028	punct	", ",Novus
R2710	T9032	T9028	npadvmod	CO,Novus
R2711	T9033	T9023	punct	;,H
R2712	T9034	T9023	nmod	cat.,H
R2713	T9035	T9023	punct	#,H
R2714	T9036	T9023	compound	NB730,H
R2715	T9037	T9023	punct	-,H
R2716	T9038	T9023	punct	),H
R2717	T9039	T9017	auxpass	was,used
R2718	T9040	T9017	prep	for,used
R2719	T9041	T9040	pobj	detection,for
R2720	T9042	T9017	advcl	using,used
R2721	T9043	T9044	det	the,reagent
R2722	T9044	T9042	dobj	reagent,using
R2723	T9045	T9046	compound	Western,Lightning
R2724	T9046	T9044	compound	Lightning,reagent
R2725	T9047	T9044	compound	chemiluminescence,reagent
R2726	T9048	T9049	punct	(,Elmer
R2727	T9049	T9044	parataxis	Elmer,reagent
R2728	T9050	T9049	compound	Perkin,Elmer
R2729	T9051	T9049	punct	", ",Elmer
R2730	T9052	T9049	npadvmod	Boston,Elmer
R2731	T9053	T9049	punct	", ",Elmer
R2732	T9054	T9049	npadvmod	MA,Elmer
R2733	T9055	T9049	punct	),Elmer
R2734	T9056	T9017	cc	and,used
R2735	T9057	T9017	conj	exposed,used
R2736	T9058	T9057	prep	to,exposed
R2737	T9059	T9060	compound	X-ray,film
R2738	T9060	T9058	pobj	film,to
R2739	T9061	T9017	punct	.,used
R2740	T9141	T9142	amod	Statistical,analyses
R2741	T9144	T9145	det	All,data
R2742	T9145	T9151	nsubjpass	data,presented
R2743	T9146	T9145	nmod	BCAA,data
R2744	T9147	T9146	cc	and,BCAA
R2745	T9148	T9146	conj	BCKDH,BCAA
R2746	T9149	T9145	compound	enzyme,data
R2747	T9150	T9145	compound	activity,data
R2748	T9152	T9151	auxpass	are,presented
R2749	T9153	T9151	prep	as,presented
R2750	T9154	T9155	det	the,mean
R2751	T9155	T9153	pobj	mean,as
R2752	T9156	T9155	cc	+,mean
R2753	T9157	T9156	punct	/,+
R2754	T9158	T9156	punct	-,+
R2755	T9159	T9160	det	the,error
R2756	T9160	T9155	conj	error,mean
R2757	T9161	T9160	amod	standard,error
R2758	T9162	T9160	prep	of,error
R2759	T9163	T9164	det	the,mean
R2760	T9164	T9162	pobj	mean,of
R2761	T9165	T9160	punct	(,error
R2762	T9166	T9160	appos	S.E.M.,error
R2763	T9167	T9151	punct	),presented
R2764	T9168	T9151	punct	.,presented
R2765	T9170	T9171	nsubjpass	Differences,compared
R2766	T9172	T9170	prep	between,Differences
R2767	T9173	T9172	pobj	genotypes,between
R2768	T9174	T9171	auxpass	were,compared
R2769	T9175	T9171	prep	by,compared
R2770	T9176	T9177	poss	Student,test
R2771	T9177	T9175	pobj	test,by
R2772	T9178	T9176	case	's,Student
R2773	T9179	T9177	compound	t,test
R2774	T9180	T9181	punct	[,32
R2775	T9181	T9171	parataxis	32,compared
R2776	T9182	T9181	punct	],32
R2777	T9183	T9171	punct	.,compared
R2778	T10368	T10367	prep	of,Production
R2779	T10369	T10370	compound	E2,mice
R2780	T10370	T10368	pobj	mice,of
R2781	T10371	T10372	compound	gene,knockout
R2782	T10372	T10370	compound	knockout,mice
R2783	T10374	T10375	aux	To,create
R2784	T10375	T10376	advcl	create,used
R2785	T10377	T10378	compound	E2,mice
R2786	T10378	T10375	dobj	mice,create
R2787	T10379	T10378	compound	knockout,mice
R2788	T10380	T10376	punct	", ",used
R2789	T10381	T10376	nsubj	we,used
R2790	T10382	T10383	compound	gene,targeting
R2791	T10383	T10376	dobj	targeting,used
R2792	T10384	T10376	prep	in,used
R2793	T10385	T10386	compound	mouse,cells
R2794	T10386	T10384	pobj	cells,in
R2795	T10387	T10386	compound	ES,cells
R2796	T10388	T10389	aux	to,disrupt
R2797	T10389	T10376	advcl	disrupt,used
R2798	T10390	T10391	det	the,gene
R2799	T10391	T10389	dobj	gene,disrupt
R2800	T10392	T10391	compound	E2,gene
R2801	T10393	T10376	punct	.,used
R2802	T10395	T10396	det	The,strategy
R2803	T10396	T10398	nsubjpass	strategy,illustrated
R2804	T10397	T10396	amod	overall,strategy
R2805	T10399	T10396	prep	for,strategy
R2806	T10400	T10399	pcomp	disrupting,for
R2807	T10401	T10402	det	the,gene
R2808	T10402	T10400	dobj	gene,disrupting
R2809	T10403	T10402	compound	E2,gene
R2810	T10404	T10398	auxpass	is,illustrated
R2811	T10405	T10398	prep	in,illustrated
R2812	T10406	T10407	compound	Fig.,1A
R2813	T10407	T10405	pobj	1A,in
R2814	T10408	T10398	punct	.,illustrated
R2815	T10410	T10411	det	The,construct
R2816	T10411	T10414	nsubjpass	construct,designed
R2817	T10412	T10413	compound	gene,targeting
R2818	T10413	T10411	compound	targeting,construct
R2819	T10415	T10414	auxpass	was,designed
R2820	T10416	T10417	aux	to,replace
R2821	T10417	T10414	advcl	replace,designed
R2822	T10418	T10419	det	a,fragment
R2823	T10419	T10417	dobj	fragment,replace
R2824	T10420	T10421	nummod	1.67,kb
R2825	T10421	T10419	nmod	kb,fragment
R2826	T10422	T10423	nmod	EcoRV,Smal
R2827	T10423	T10419	nmod	Smal,fragment
R2828	T10424	T10423	punct	/,Smal
R2829	T10425	T10419	amod	genomic,fragment
R2830	T10426	T10419	compound	DNA,fragment
R2831	T10427	T10419	acl	encompassing,fragment
R2832	T10428	T10427	dobj	part,encompassing
R2833	T10429	T10428	prep	of,part
R2834	T10430	T10429	pobj	Exon,of
R2835	T10431	T10430	nummod	4,Exon
R2836	T10432	T10428	cc	and,part
R2837	T10433	T10428	conj	all,part
R2838	T10434	T10433	prep	of,all
R2839	T10435	T10434	pobj	Exon,of
R2840	T10436	T10435	nummod	5,Exon
R2841	T10437	T10417	prep	with,replace
R2842	T10438	T10439	det	the,cassette
R2843	T10439	T10437	pobj	cassette,with
R2844	T10440	T10439	nmod	PGKneo,cassette
R2845	T10441	T10439	amod	selectable,cassette
R2846	T10442	T10439	compound	marker,cassette
R2847	T10443	T10414	punct	.,designed
R2848	T10445	T10446	prep	Of,displayed
R2849	T10447	T10448	nummod	522,clones
R2850	T10448	T10445	pobj	clones,Of
R2851	T10449	T10450	compound	ES,cell
R2852	T10450	T10448	compound	cell,clones
R2853	T10451	T10448	acl	screened,clones
R2854	T10452	T10451	prep	for,screened
R2855	T10453	T10452	pobj	targeting,for
R2856	T10454	T10451	prep	by,screened
R2857	T10455	T10456	compound	Southern,blot
R2858	T10456	T10457	compound	blot,analysis
R2859	T10457	T10454	pobj	analysis,by
R2860	T10458	T10446	punct	", ",displayed
R2861	T10459	T10446	nsubj	29,displayed
R2862	T10460	T10461	punct	(,%
R2863	T10461	T10459	parataxis	%,29
R2864	T10462	T10461	nummod	5,%
R2865	T10463	T10461	punct	),%
R2866	T10464	T10465	det	the,polymorphisms
R2867	T10465	T10446	dobj	polymorphisms,displayed
R2868	T10466	T10465	amod	predicted,polymorphisms
R2869	T10467	T10468	compound	restriction,length
R2870	T10468	T10465	compound	length,polymorphisms
R2871	T10469	T10468	compound	fragment,length
R2872	T10470	T10465	amod	indicative,polymorphisms
R2873	T10471	T10470	prep	of,indicative
R2874	T10472	T10471	pobj	gene,of
R2875	T10473	T10472	amod	targeting,gene
R2876	T10474	T10446	prep	at,displayed
R2877	T10475	T10476	det	the,locus
R2878	T10476	T10474	pobj	locus,at
R2879	T10477	T10476	compound	E2,locus
R2880	T10478	T10446	punct	.,displayed
R2881	T10480	T10481	mark	As,illustrated
R2882	T10481	T10482	advcl	illustrated,hybridizes
R2883	T10483	T10481	prep	in,illustrated
R2884	T10484	T10485	compound	Fig.,1A
R2885	T10485	T10483	pobj	1A,in
R2886	T10486	T10485	cc	and,1A
R2887	T10487	T10485	conj	1B,1A
R2888	T10488	T10482	punct	", ",hybridizes
R2889	T10489	T10490	det	an,probe
R2890	T10490	T10482	nsubj	probe,hybridizes
R2891	T10491	T10490	nmod	E2,probe
R2892	T10492	T10490	nmod	Exon,probe
R2893	T10493	T10492	nummod	6,Exon
R2894	T10494	T10490	amod	specific,probe
R2895	T10495	T10490	punct	", ",probe
R2896	T10496	T10497	dep	which,is
R2897	T10497	T10490	relcl	is,probe
R2898	T10498	T10497	acomp	external,is
R2899	T10499	T10498	prep	to,external
R2900	T10500	T10501	det	the,construct
R2901	T10501	T10499	pobj	construct,to
R2902	T10502	T10501	compound	targeting,construct
R2903	T10503	T10482	punct	", ",hybridizes
R2904	T10504	T10482	prep	to,hybridizes
R2905	T10505	T10506	advmod	only,fragment
R2906	T10506	T10504	pobj	fragment,to
R2907	T10507	T10506	det	a,fragment
R2908	T10508	T10509	punct	~,16
R2909	T10509	T10510	nummod	16,kb
R2910	T10510	T10506	compound	kb,fragment
R2911	T10511	T10506	compound	BglI,fragment
R2912	T10512	T10506	compound	restriction,fragment
R2913	T10513	T10506	prep	from,fragment
R2914	T10514	T10515	det	the,allele
R2915	T10515	T10513	pobj	allele,from
R2916	T10516	T10517	amod	wild,type
R2917	T10517	T10515	compound	type,allele
R2918	T10518	T10515	prep	in,allele
R2919	T10519	T10520	det	the,line
R2920	T10520	T10518	pobj	line,in
R2921	T10521	T10520	amod	parental,line
R2922	T10522	T10520	compound	R1,line
R2923	T10523	T10524	compound	ES,cell
R2924	T10524	T10520	compound	cell,line
R2925	T10525	T10482	punct	.,hybridizes
R2926	T10527	T10528	prep	In,hybridizes
R2927	T10529	T10530	advmod	correctly,targeted
R2928	T10530	T10531	amod	targeted,cells
R2929	T10531	T10527	pobj	cells,In
R2930	T10532	T10531	compound	ES,cells
R2931	T10533	T10528	punct	", ",hybridizes
R2932	T10534	T10535	det	this,probe
R2933	T10535	T10528	nsubj	probe,hybridizes
R2934	T10536	T10528	advmod	also,hybridizes
R2935	T10537	T10528	prep	to,hybridizes
R2936	T10538	T10539	det	a,fragment
R2937	T10539	T10537	pobj	fragment,to
R2938	T10540	T10541	punct	~,11
R2939	T10541	T10542	nummod	11,kb
R2940	T10542	T10539	compound	kb,fragment
R2941	T10543	T10539	compound	BglI,fragment
R2942	T10544	T10539	compound	restriction,fragment
R2943	T10545	T10528	punct	.,hybridizes
R2944	T10547	T10548	nsubjpass	Targeting,confirmed
R2945	T10549	T10548	auxpass	was,confirmed
R2946	T10550	T10548	prep	with,confirmed
R2947	T10551	T10552	amod	several,enzymes
R2948	T10552	T10550	pobj	enzymes,with
R2949	T10553	T10552	amod	additional,enzymes
R2950	T10554	T10552	compound	restriction,enzymes
R2951	T10555	T10552	cc	and,enzymes
R2952	T10556	T10552	conj	probes,enzymes
R2953	T10557	T10558	punct	(,shown
R2954	T10558	T10548	parataxis	shown,confirmed
R2955	T10559	T10558	nsubj	data,shown
R2956	T10560	T10558	neg	not,shown
R2957	T10561	T10558	punct	),shown
R2958	T10562	T10548	punct	.,confirmed
R2959	T10564	T10565	advmod	Correctly,targeted
R2960	T10565	T10566	amod	targeted,cells
R2961	T10566	T10568	nsubjpass	cells,microinjected
R2962	T10567	T10566	compound	ES,cells
R2963	T10569	T10568	auxpass	were,microinjected
R2964	T10570	T10568	prep	into,microinjected
R2965	T10571	T10570	pobj	blastocysts,into
R2966	T10572	T10573	aux	to,produce
R2967	T10573	T10568	advcl	produce,microinjected
R2968	T10574	T10575	amod	chimeric,mice
R2969	T10575	T10573	dobj	mice,produce
R2970	T10576	T10568	punct	.,microinjected
R2971	T10578	T10579	nsubjpass	Chimerics,bred
R2972	T10580	T10579	auxpass	were,bred
R2973	T10581	T10579	prep	to,bred
R2974	T10582	T10583	compound	C57BL,6J
R2975	T10583	T10585	compound	6J,mice
R2976	T10584	T10583	punct	/,6J
R2977	T10585	T10581	pobj	mice,to
R2978	T10586	T10579	punct	.,bred
R2979	T10588	T10589	prep	Following,interbred
R2980	T10590	T10591	compound	germline,transmission
R2981	T10591	T10588	pobj	transmission,Following
R2982	T10592	T10591	prep	of,transmission
R2983	T10593	T10594	det	the,allele
R2984	T10594	T10592	pobj	allele,of
R2985	T10595	T10594	amod	targeted,allele
R2986	T10596	T10589	punct	", ",interbred
R2987	T10597	T10598	amod	heterozygous,mice
R2988	T10598	T10589	nsubjpass	mice,interbred
R2989	T10599	T10589	auxpass	were,interbred
R2990	T10600	T10601	aux	to,produce
R2991	T10601	T10589	advcl	produce,interbred
R2992	T10602	T10603	amod	wild,type
R2993	T10603	T10604	nmod	type,animals
R2994	T10604	T10601	dobj	animals,produce
R2995	T10605	T10606	punct	(,+
R2996	T10606	T10603	punct	+,type
R2997	T10607	T10606	punct	+,+
R2998	T10608	T10606	punct	/,+
R2999	T10609	T10606	punct	),+
R3000	T10610	T10603	punct	", ",type
R3001	T10611	T10603	conj	heterozygous,type
R3002	T10612	T10613	punct	(,-
R3003	T10613	T10611	punct	-,heterozygous
R3004	T10614	T10613	punct	+,-
R3005	T10615	T10613	punct	/,-
R3006	T10616	T10613	punct	),-
R3007	T10617	T10611	cc	and,heterozygous
R3008	T10618	T10611	conj	homozygous,heterozygous
R3009	T10619	T10620	punct	(,-
R3010	T10620	T10618	punct	-,homozygous
R3011	T10621	T10620	punct	-,-
R3012	T10622	T10620	punct	/,-
R3013	T10623	T10620	punct	),-
R3014	T10624	T10589	punct	.,interbred
R3015	T10626	T10627	nsubjpass	Mice,genotyped
R3016	T10628	T10627	auxpass	were,genotyped
R3017	T10629	T10627	prep	by,genotyped
R3018	T10630	T10631	compound	Southern,blot
R3019	T10631	T10632	compound	blot,analysis
R3020	T10632	T10629	pobj	analysis,by
R3021	T10633	T10627	punct	.,genotyped
R3022	T10635	T10636	det	The,probe
R3023	T10636	T10640	nsubj	probe,hybridized
R3024	T10637	T10638	npadvmod	Exon,specific
R3025	T10638	T10636	amod	specific,probe
R3026	T10639	T10637	nummod	6,Exon
R3027	T10641	T10640	prep	to,hybridized
R3028	T10642	T10643	advmod	only,fragment
R3029	T10643	T10641	pobj	fragment,to
R3030	T10644	T10643	det	a,fragment
R3031	T10645	T10646	punct	~,16
R3032	T10646	T10647	nummod	16,kb
R3033	T10647	T10643	compound	kb,fragment
R3034	T10648	T10643	compound	BglI,fragment
R3035	T10649	T10643	compound	restriction,fragment
R3036	T10650	T10643	prep	in,fragment
R3037	T10651	T10652	punct	+,+
R3038	T10652	T10654	punct	+,mice
R3039	T10653	T10652	punct	/,+
R3040	T10654	T10650	pobj	mice,in
R3041	T10655	T10643	punct	", ",fragment
R3042	T10656	T10657	det	a,fragment
R3043	T10657	T10643	appos	fragment,fragment
R3044	T10658	T10659	punct	~,11
R3045	T10659	T10660	nummod	11,kb
R3046	T10660	T10657	compound	kb,fragment
R3047	T10661	T10657	compound	BglI,fragment
R3048	T10662	T10657	prep	in,fragment
R3049	T10663	T10664	punct	-,-
R3050	T10664	T10666	punct	-,mice
R3051	T10665	T10664	punct	/,-
R3052	T10666	T10662	pobj	mice,in
R3053	T10667	T10641	punct	", ",to
R3054	T10668	T10641	cc	and,to
R3055	T10669	T10641	conj	to,to
R3056	T10670	T10669	pobj	both,to
R3057	T10671	T10670	prep	of,both
R3058	T10672	T10673	det	these,fragments
R3059	T10673	T10671	pobj	fragments,of
R3060	T10674	T10670	prep	in,both
R3061	T10675	T10676	punct	+,-
R3062	T10676	T10678	punct	-,mice
R3063	T10677	T10676	punct	/,-
R3064	T10678	T10674	pobj	mice,in
R3065	T10679	T10680	punct	(,1B
R3066	T10680	T10640	parataxis	1B,hybridized
R3067	T10681	T10680	compound	Fig.,1B
R3068	T10682	T10680	punct	),1B
R3069	T10683	T10640	punct	.,hybridized
R3070	T10685	T10686	nsubjpass	Mice,born
R3071	T10687	T10685	amod	homozygous,Mice
R3072	T10688	T10687	prep	for,homozygous
R3073	T10689	T10690	det	the,mutation
R3074	T10690	T10688	pobj	mutation,for
R3075	T10691	T10690	compound	E2,mutation
R3076	T10692	T10686	auxpass	were,born
R3077	T10693	T10686	prep	at,born
R3078	T10694	T10695	det	the,frequency
R3079	T10695	T10693	pobj	frequency,at
R3080	T10696	T10695	amod	expected,frequency
R3081	T10697	T10686	punct	.,born
R3082	T10699	T10700	compound	Genotype,analysis
R3083	T10700	T10701	nsubj	analysis,revealed
R3084	T10702	T10700	prep	of,analysis
R3085	T10703	T10702	pobj	pups,of
R3086	T10704	T10703	acl	derived,pups
R3087	T10705	T10704	prep	from,derived
R3088	T10706	T10707	punct	+,-
R3089	T10707	T10709	punct	-,matings
R3090	T10708	T10707	punct	/,-
R3091	T10709	T10705	pobj	matings,from
R3092	T10710	T10707	prep	by,-
R3093	T10711	T10712	punct	+,-
R3094	T10712	T10710	punct	-,by
R3095	T10713	T10712	punct	/,-
R3096	T10714	T10715	mark	that,were
R3097	T10715	T10701	ccomp	were,revealed
R3098	T10716	T10717	punct	+,+
R3099	T10717	T10719	punct	+,mice
R3100	T10718	T10717	punct	/,+
R3101	T10719	T10715	nsubj	mice,were
R3102	T10720	T10717	punct	", ",+
R3103	T10721	T10722	punct	+,-
R3104	T10722	T10717	conj	-,+
R3105	T10723	T10722	punct	/,-
R3106	T10724	T10722	punct	", ",-
R3107	T10725	T10722	cc	and,-
R3108	T10726	T10727	punct	-,-
R3109	T10727	T10722	conj	-,-
R3110	T10728	T10727	punct	/,-
R3111	T10729	T10715	acomp	present,were
R3112	T10730	T10715	prep	at,were
R3113	T10731	T10732	advmod	nearly,frequency
R3114	T10732	T10730	pobj	frequency,at
R3115	T10733	T10732	det	the,frequency
R3116	T10734	T10732	amod	expected,frequency
R3117	T10735	T10736	nummod	1,1
R3118	T10736	T10732	nummod	1,frequency
R3119	T10737	T10736	punct	:,1
R3120	T10738	T10736	nummod	2,1
R3121	T10739	T10736	punct	:,1
R3122	T10740	T10701	punct	.,revealed
R3123	T10742	T10743	prep	Of,were
R3124	T10744	T10745	det	the,animals
R3125	T10745	T10742	pobj	animals,Of
R3126	T10746	T10745	amod	initial,animals
R3127	T10747	T10745	nummod	60,animals
R3128	T10748	T10745	acl	genotyped,animals
R3129	T10749	T10743	punct	", ",were
R3130	T10750	T10743	nsubj	19,were
R3131	T10751	T10752	punct	(,%
R3132	T10752	T10750	parataxis	%,19
R3133	T10753	T10752	nummod	32,%
R3134	T10754	T10752	punct	),%
R3135	T10755	T10756	punct	+,+
R3136	T10756	T10743	attr	+,were
R3137	T10757	T10756	punct	/,+
R3138	T10758	T10743	punct	", ",were
R3139	T10759	T10760	nsubj	27,were
R3140	T10760	T10743	conj	were,were
R3141	T10761	T10762	punct	(,%
R3142	T10762	T10759	parataxis	%,27
R3143	T10763	T10762	nummod	45,%
R3144	T10764	T10762	punct	),%
R3145	T10765	T10766	punct	+,-
R3146	T10766	T10760	attr	-,were
R3147	T10767	T10766	punct	/,-
R3148	T10768	T10760	punct	", ",were
R3149	T10769	T10760	cc	and,were
R3150	T10770	T10771	nsubj	14,were
R3151	T10771	T10760	conj	were,were
R3152	T10772	T10773	punct	(,%
R3153	T10773	T10770	parataxis	%,14
R3154	T10774	T10773	nummod	23,%
R3155	T10775	T10773	punct	),%
R3156	T10776	T10777	punct	-,-
R3157	T10777	T10771	attr	-,were
R3158	T10778	T10777	punct	/,-
R3159	T10779	T10743	punct	.,were
R3160	T10781	T10782	advmod	Thus,was
R3161	T10783	T10782	punct	", ",was
R3162	T10784	T10785	det	the,gene
R3163	T10785	T10782	nsubj	gene,was
R3164	T10786	T10785	compound	E2,gene
R3165	T10787	T10782	acomp	dispensable,was
R3166	T10788	T10787	prep	for,dispensable
R3167	T10789	T10790	amod	normal,development
R3168	T10790	T10788	pobj	development,for
R3169	T10791	T10790	amod	embryonic,development
R3170	T10792	T10782	punct	.,was
R3171	T10794	T10795	advmod	However,died
R3172	T10796	T10795	punct	", ",died
R3173	T10797	T10798	mark	as,expected
R3174	T10798	T10795	advcl	expected,died
R3175	T10799	T10795	punct	", ",died
R3176	T10800	T10801	advmod	nearly,mice
R3177	T10801	T10795	nsubj	mice,died
R3178	T10802	T10801	det	all,mice
R3179	T10803	T10801	amod	homozygous,mice
R3180	T10804	T10795	prep	in,died
R3181	T10805	T10806	det	the,period
R3182	T10806	T10804	pobj	period,in
R3183	T10807	T10806	amod	perinatal,period
R3184	T10808	T10795	punct	.,died
R3185	T10810	T10811	advmod	Immediately,following
R3186	T10811	T10812	prep	following,were
R3187	T10812	T10817	ccomp	were,were
R3188	T10813	T10811	pobj	birth,following
R3189	T10814	T10812	punct	", ",were
R3190	T10815	T10816	amod	homozygous,pups
R3191	T10816	T10812	nsubj	pups,were
R3192	T10818	T10812	acomp	indistinguishable,were
R3193	T10819	T10818	prep	from,indistinguishable
R3194	T10820	T10821	poss	their,littermates
R3195	T10821	T10819	pobj	littermates,from
R3196	T10822	T10823	punct	+,+
R3197	T10823	T10821	punct	+,littermates
R3198	T10824	T10823	punct	/,+
R3199	T10825	T10823	cc	and,+
R3200	T10826	T10827	punct	+,-
R3201	T10827	T10823	conj	-,+
R3202	T10828	T10827	punct	/,-
R3203	T10829	T10817	punct	;,were
R3204	T10830	T10817	nsubj	they,were
R3205	T10831	T10817	acomp	vigorous,were
R3206	T10832	T10831	punct	", ",vigorous
R3207	T10833	T10831	conj	active,vigorous
R3208	T10834	T10833	cc	and,active
R3209	T10835	T10833	conj	able,active
R3210	T10836	T10837	aux	to,suckle
R3211	T10837	T10835	xcomp	suckle,able
R3212	T10838	T10817	punct	.,were
R3213	T10840	T10841	prep	By,became
R3214	T10842	T10843	amod	mid,day
R3215	T10843	T10840	pobj	day,By
R3216	T10844	T10842	prep	to,mid
R3217	T10845	T10844	amod	late,to
R3218	T10846	T10843	prep	on,day
R3219	T10847	T10848	amod	postnatal,day
R3220	T10848	T10846	pobj	day,on
R3221	T10849	T10848	nummod	one,day
R3222	T10850	T10841	punct	", ",became
R3223	T10851	T10852	advmod	most,pups
R3224	T10852	T10841	nsubj	pups,became
R3225	T10853	T10854	punct	-,-
R3226	T10854	T10852	punct	-,pups
R3227	T10855	T10854	punct	/,-
R3228	T10856	T10841	acomp	moribund,became
R3229	T10857	T10841	cc	and,became
R3230	T10858	T10841	conj	were,became
R3231	T10859	T10860	advmod	readily,identifiable
R3232	T10860	T10858	acomp	identifiable,were
R3233	T10861	T10862	mark	as,were
R3234	T10862	T10860	advcl	were,identifiable
R3235	T10863	T10862	nsubj	they,were
R3236	T10864	T10865	amod	lethargic,pale
R3237	T10865	T10862	acomp	pale,were
R3238	T10866	T10865	punct	", ",pale
R3239	T10867	T10862	punct	", ",were
R3240	T10868	T10862	cc	and,were
R3241	T10869	T10862	conj	exhibited,were
R3242	T10870	T10871	amod	gasping,movements
R3243	T10871	T10869	dobj	movements,exhibited
R3244	T10872	T10871	amod	respiratory,movements
R3245	T10873	T10841	punct	.,became
R3246	T10875	T10876	prep	With,died
R3247	T10877	T10878	amod	few,exceptions
R3248	T10878	T10875	pobj	exceptions,With
R3249	T10879	T10876	punct	", ",died
R3250	T10880	T10881	punct	-,-
R3251	T10881	T10883	punct	-,pups
R3252	T10882	T10881	punct	/,-
R3253	T10883	T10876	nsubj	pups,died
R3254	T10884	T10876	prep	within,died
R3255	T10885	T10886	nummod	72,hours
R3256	T10886	T10884	pobj	hours,within
R3257	T10887	T10886	prep	of,hours
R3258	T10888	T10887	pobj	birth,of
R3259	T10889	T10876	punct	.,died
R3260	T10891	T10892	nsubj	We,observed
R3261	T10893	T10892	aux	have,observed
R3262	T10894	T10895	nummod	one,pup
R3263	T10895	T10892	dobj	pup,observed
R3264	T10896	T10895	amod	rare,pup
R3265	T10897	T10898	punct	-,-
R3266	T10898	T10895	punct	-,pup
R3267	T10899	T10898	punct	/,-
R3268	T10900	T10901	dep	that,survived
R3269	T10901	T10895	relcl	survived,pup
R3270	T10902	T10901	prep	to,survived
R3271	T10903	T10904	amod	postnatal,day
R3272	T10904	T10902	pobj	day,to
R3273	T10905	T10904	nummod	13,day
R3274	T10906	T10892	punct	.,observed
R3275	T10908	T10909	det	The,reason
R3276	T10909	T10910	nsubj	reason,is
R3277	T10911	T10909	prep	for,reason
R3278	T10912	T10913	det	the,survival
R3279	T10913	T10911	pobj	survival,for
R3280	T10914	T10913	amod	prolonged,survival
R3281	T10915	T10913	prep	of,survival
R3282	T10916	T10917	det	this,pup
R3283	T10917	T10915	pobj	pup,of
R3284	T10918	T10910	acomp	unknown,is
R3285	T10919	T10910	punct	.,is
R3290	T12206	T12207	npadvmod	E2,deficient
R3291	T12207	T12208	amod	deficient,mice
R3292	T12208	T12209	nsubj	mice,model
R3293	T12210	T12209	advmod	accurately,model
R3294	T12211	T12212	amod	classic,MSUD
R3295	T12212	T12209	dobj	MSUD,model
R3296	T12214	T12215	aux	To,demonstrate
R3297	T12215	T12216	advcl	demonstrate,determined
R3298	T12217	T12218	mark	that,created
R3299	T12218	T12215	ccomp	created,demonstrate
R3300	T12219	T12220	det	the,event
R3301	T12220	T12218	nsubj	event,created
R3302	T12221	T12222	compound	gene,targeting
R3303	T12222	T12220	compound	targeting,event
R3304	T12223	T12224	det	a,allele
R3305	T12224	T12218	dobj	allele,created
R3306	T12225	T12224	amod	true,allele
R3307	T12226	T12227	npadvmod	E2,null
R3308	T12227	T12224	amod	null,allele
R3309	T12228	T12216	punct	", ",determined
R3310	T12229	T12216	nsubj	we,determined
R3311	T12230	T12231	compound	BCKDH,activity
R3312	T12231	T12216	dobj	activity,determined
R3313	T12232	T12216	prep	in,determined
R3314	T12233	T12234	compound	liver,homogenates
R3315	T12234	T12232	pobj	homogenates,in
R3316	T12235	T12234	prep	of,homogenates
R3317	T12236	T12237	amod	postnatal,day
R3318	T12237	T12238	nmod	day,pups
R3319	T12238	T12235	pobj	pups,of
R3320	T12239	T12237	nummod	1,day
R3321	T12240	T12238	compound	mouse,pups
R3322	T12241	T12238	acl	derived,pups
R3323	T12242	T12241	prep	from,derived
R3324	T12243	T12244	punct	+,-
R3325	T12244	T12246	punct	-,pairs
R3326	T12245	T12244	punct	/,-
R3327	T12246	T12242	pobj	pairs,from
R3328	T12247	T12244	prep	by,-
R3329	T12248	T12249	punct	+,-
R3330	T12249	T12247	punct	-,by
R3331	T12250	T12249	punct	/,-
R3332	T12251	T12246	compound	mating,pairs
R3333	T12252	T12216	punct	.,determined
R3334	T12254	T12255	mark	As,shown
R3335	T12255	T12256	advcl	shown,was
R3336	T12257	T12255	prep	in,shown
R3337	T12258	T12259	compound	Figure,2A
R3338	T12259	T12257	pobj	2A,in
R3339	T12260	T12256	punct	", ",was
R3340	T12261	T12262	det	the,activity
R3341	T12262	T12256	nsubj	activity,was
R3342	T12263	T12262	compound	BCKDH,activity
R3343	T12264	T12262	prep	in,activity
R3344	T12265	T12266	punct	+,+
R3346	T12267	T12266	punct	/,+
R3363	T12286	T12282	pobj	livers,in
R3364	T12287	T12286	compound	mouse,livers
R3365	T12288	T12274	punct	.,was
R3366	T12290	T12291	mark	As,expected
R3367	T12291	T12292	advcl	expected,had
R3368	T12293	T12292	punct	", ",had
R3369	T12294	T12292	nsubj	homogenates,had
R3370	T12295	T12294	prep	from,homogenates
R3371	T12296	T12297	punct	+,-
R3372	T12297	T12299	punct	-,mice
R3373	T12298	T12297	punct	/,-
R3374	T12299	T12295	pobj	mice,from
R3375	T12300	T12301	advmod	approximately,half
R3376	T12301	T12302	nummod	half,activity
R3377	T12302	T12292	dobj	activity,had
R3378	T12303	T12302	det	the,activity
R3379	T12304	T12302	prep	of,activity
R3380	T12305	T12306	poss	their,littermates
R3381	T12306	T12304	pobj	littermates,of
R3382	T12307	T12308	punct	+,+
R3383	T12308	T12306	punct	+,littermates
R3384	T12309	T12308	punct	/,+
R3385	T12310	T12311	punct	(,2A
R3386	T12311	T12292	parataxis	2A,had
R3387	T12312	T12311	compound	Figure,2A
R3388	T12313	T12311	punct	),2A
R3389	T12314	T12292	punct	.,had
R3390	T12316	T12317	det	The,results
R3391	T12317	T12318	nsubj	results,are
R3392	T12319	T12317	prep	from,results
R3393	T12320	T12321	punct	-,-
R3394	T12321	T12323	punct	-,mice
R3395	T12322	T12321	punct	/,-
R3396	T12323	T12319	pobj	mice,from
R3397	T12324	T12318	acomp	similar,are
R3398	T12325	T12324	prep	to,similar
R3399	T12326	T12325	pobj	that,to
R3400	T12327	T12326	acl	observed,that
R3401	T12328	T12327	prep	in,observed
R3402	T12329	T12328	pobj	humans,in
R3403	T12330	T12329	prep	with,humans
R3404	T12331	T12332	amod	classic,MSUD
R3405	T12332	T12330	pobj	MSUD,with
R3406	T12333	T12334	punct	[,1
R3407	T12334	T12318	parataxis	1,are
R3408	T12335	T12334	punct	],1
R3409	T12336	T12318	punct	.,are
R3420	T12350	T12348	dobj	protein,examine
R3421	T12351	T12348	prep	in,examine
R3422	T12352	T12353	det	the,mice
R3423	T12353	T12351	pobj	mice,in
R3424	T12354	T12340	punct	.,used
R3425	T12356	T12357	mark	As,shown
R3426	T12357	T12358	advcl	shown,was
R3427	T12359	T12357	prep	in,shown
R3428	T12360	T12361	compound	Figure,1C
R3429	T12361	T12359	pobj	1C,in
R3430	T12362	T12361	cc	and,1C
R3431	T12363	T12361	conj	1D,1C
R3432	T12364	T12358	punct	", ",was
R3433	T12365	T12366	amod	immunoreactive,protein
R3434	T12366	T12358	nsubj	protein,was
R3435	T12367	T12366	compound	E2,protein
R3436	T12368	T12358	acomp	abundant,was
R3437	T12369	T12358	prep	in,was
R3438	T12370	T12369	pobj	liver,in
R3439	T12371	T12370	cc	and,liver
R3440	T12372	T12373	amod	embryonic,fibroblasts
R3441	T12373	T12370	conj	fibroblasts,liver
R3442	T12374	T12370	prep	of,liver
R3443	T12375	T12376	punct	+,+
R3444	T12376	T12378	punct	+,mice
R3445	T12377	T12376	punct	/,+
R3446	T12378	T12374	pobj	mice,of
R3447	T12379	T12358	punct	.,was
R3448	T12381	T12382	prep	In,was
R3449	T12383	T12384	amod	marked,contrast
R3450	T12384	T12381	pobj	contrast,In
R3451	T12385	T12382	punct	", ",was
R3452	T12386	T12387	amod	immunoreactive,protein
R3453	T12387	T12382	nsubj	protein,was
R3454	T12388	T12387	compound	E2,protein
R3455	T12389	T12382	acomp	absent,was
R3456	T12390	T12382	prep	in,was
R3457	T12391	T12392	det	these,tissues
R3458	T12392	T12390	pobj	tissues,in
R3459	T12393	T12392	amod	same,tissues
R3460	T12394	T12392	prep	of,tissues
R3461	T12395	T12396	punct	-,-
R3462	T12396	T12398	punct	-,mice
R3463	T12397	T12396	punct	/,-
R3464	T12398	T12394	pobj	mice,of
R3465	T12399	T12382	punct	.,was
R3466	T12401	T12402	amod	Homozygous,knockout
R3467	T12402	T12404	compound	knockout,mice
R3468	T12403	T12402	compound	E2,knockout
R3469	T12404	T12405	nsubj	mice,had
R3470	T12406	T12407	det	a,increase
R3471	T12407	T12405	dobj	increase,had
R3472	T12408	T12409	advmod	nearly,3
R3473	T12409	T12410	quantmod	3,fold
R3474	T12410	T12407	nummod	fold,increase
R3475	T12411	T12410	punct	-,fold
R3476	T12412	T12407	prep	in,increase
R3477	T12413	T12414	nmod	blood,levels
R3478	T12414	T12412	pobj	levels,in
R3479	T12415	T12416	punct	(,2B
R3480	T12416	T12413	parataxis	2B,blood
R3481	T12417	T12416	compound	Figure,2B
R3482	T12418	T12416	punct	),2B
R3483	T12419	T12413	cc	and,blood
R3484	T12420	T12413	conj	urine,blood
R3485	T12421	T12422	punct	(,shown
R3486	T12422	T12420	parataxis	shown,urine
R3487	T12423	T12422	nsubj	data,shown
R3488	T12424	T12422	neg	not,shown
R3489	T12425	T12422	punct	),shown
R3490	T12426	T12414	prep	of,levels
R3491	T12427	T12426	pobj	BCAA,of
R3492	T12428	T12429	punct	(,sum
R3493	T12429	T12427	parataxis	sum,BCAA
R3494	T12430	T12429	prep	of,sum
R3495	T12431	T12430	pobj	leucine,of
R3496	T12432	T12431	punct	", ",leucine
R3497	T12433	T12431	conj	isoleucine,leucine
R3498	T12434	T12433	punct	", ",isoleucine
R3499	T12435	T12433	cc	and,isoleucine
R3500	T12436	T12433	conj	valine,isoleucine
R3501	T12437	T12429	punct	),sum
R3502	T12438	T12407	prep	as,increase
R3503	T12439	T12438	prep	compared,as
R3504	T12440	T12439	prep	to,compared
R3505	T12441	T12442	poss	their,littermates
R3506	T12442	T12440	pobj	littermates,to
R3507	T12443	T12444	punct	+,+
R3508	T12444	T12442	punct	+,littermates
R3509	T12445	T12444	punct	/,+
R3510	T12446	T12405	punct	.,had
R3511	T12448	T12449	mark	Because,analyzed
R3512	T12449	T12453	advcl	analyzed,include
R3513	T12450	T12451	compound	amino,acids
R3514	T12451	T12449	nsubjpass	acids,analyzed
R3515	T12452	T12449	auxpass	were,analyzed
R3516	T12454	T12449	prep	by,analyzed
R3517	T12455	T12456	compound	tandem,spectrometry
R3518	T12456	T12454	pobj	spectrometry,by
R3519	T12457	T12456	compound	mass,spectrometry
R3520	T12458	T12453	punct	", ",include
R3521	T12459	T12460	det	the,sum
R3522	T12460	T12453	nsubj	sum,include
R3523	T12461	T12460	prep	of,sum
R3524	T12462	T12461	pobj	BCAA,of
R3525	T12463	T12460	acl	shown,sum
R3526	T12464	T12463	prep	in,shown
R3527	T12465	T12466	compound	Figure,2B
R3528	T12466	T12464	pobj	2B,in
R3529	T12467	T12453	advmod	also,include
R3530	T12468	T12453	aux	may,include
R3531	T12469	T12453	dobj	alloisoleucine,include
R3532	T12470	T12471	dep	that,produced
R3533	T12471	T12469	relcl	produced,alloisoleucine
R3534	T12472	T12471	aux	may,produced
R3535	T12473	T12471	aux	have,produced
R3536	T12474	T12471	auxpass	been,produced
R3537	T12475	T12471	prep	in,produced
R3538	T12476	T12477	punct	-,-
R3539	T12477	T12479	punct	-,mice
R3540	T12478	T12477	punct	/,-
R3541	T12479	T12475	pobj	mice,in
R3542	T12480	T12479	compound	MSUD,mice
R3543	T12481	T12453	punct	.,include
R3544	T12483	T12484	det	The,metabolism
R3545	T12484	T12485	nsubjpass	metabolism,linked
R3546	T12486	T12484	prep	of,metabolism
R3547	T12487	T12486	pobj	BCAA,of
R3548	T12488	T12485	auxpass	is,linked
R3549	T12489	T12485	prep	with,linked
R3550	T12490	T12491	det	the,synthesis
R3551	T12491	T12489	pobj	synthesis,with
R3552	T12492	T12491	prep	of,synthesis
R3553	T12493	T12492	pobj	alanine,of
R3554	T12494	T12493	punct	", ",alanine
R3555	T12495	T12493	conj	glutamate,alanine
R3556	T12496	T12495	punct	", ",glutamate
R3557	T12497	T12495	cc	and,glutamate
R3558	T12498	T12495	conj	glutamine,glutamate
R3559	T12499	T12500	punct	[,33
R3560	T12500	T12485	parataxis	33,linked
R3561	T12501	T12500	punct	],33
R3562	T12502	T12485	punct	.,linked
R3563	T12504	T12505	prep	Because,analyzed
R3564	T12506	T12504	pcomp	of,Because
R3565	T12507	T12508	amod	impaired,metabolism
R3566	T12508	T12504	pobj	metabolism,Because
R3567	T12509	T12508	prep	of,metabolism
R3568	T12510	T12509	pobj	BCAA,of
R3569	T12511	T12508	prep	in,metabolism
R3570	T12512	T12513	compound	MSUD,mice
R3571	T12513	T12511	pobj	mice,in
R3572	T12514	T12504	punct	", ",Because
R3573	T12515	T12504	cc	and,Because
R3574	T12516	T12517	aux	to,characterize
R3575	T12517	T12504	conj	characterize,Because
R3576	T12518	T12517	advmod	further,characterize
R3577	T12519	T12520	det	the,biochemistry
R3578	T12520	T12517	dobj	biochemistry,characterize
R3579	T12521	T12520	amod	abnormal,biochemistry
R3580	T12522	T12517	prep	in,characterize
R3581	T12523	T12524	det	this,model
R3582	T12524	T12522	pobj	model,in
R3583	T12525	T12505	punct	", ",analyzed
R3584	T12526	T12505	nsubj	we,analyzed
R3585	T12527	T12528	det	the,levels
R3586	T12528	T12505	dobj	levels,analyzed
R3587	T12529	T12528	compound	blood,levels
R3588	T12530	T12528	prep	of,levels
R3589	T12531	T12532	det	the,alanine
R3590	T12532	T12530	pobj	alanine,of
R3591	T12533	T12532	punct	", ",alanine
R3592	T12534	T12532	conj	glutamate,alanine
R3593	T12535	T12534	punct	", ",glutamate
R3594	T12536	T12534	cc	and,glutamate
R3595	T12537	T12534	conj	glutamine,glutamate
R3596	T12538	T12505	punct	.,analyzed
R3597	T12540	T12541	mark	As,shown
R3598	T12541	T12542	advcl	shown,were
R3599	T12543	T12541	prep	in,shown
R3600	T12544	T12543	pobj	Table,in
R3601	T12545	T12544	nummod	1,Table
R3602	T12546	T12542	punct	", ",were
R3603	T12547	T12548	det	the,levels
R3604	T12548	T12542	nsubj	levels,were
R3605	T12549	T12548	prep	of,levels
R3606	T12550	T12551	det	all,acids
R3607	T12551	T12549	pobj	acids,of
R3608	T12552	T12551	nummod	three,acids
R3609	T12553	T12551	compound	amino,acids
R3610	T12554	T12548	prep	in,levels
R3611	T12555	T12556	amod	homozygous,mice
R3612	T12556	T12554	pobj	mice,in
R3613	T12557	T12558	advmod	markedly,lower
R3614	T12558	T12542	acomp	lower,were
R3615	T12559	T12558	prep	than,lower
R3616	T12560	T12561	det	the,levels
R3617	T12561	T12559	pobj	levels,than
R3618	T12562	T12561	prep	in,levels
R3619	T12563	T12564	punct	+,+
R3620	T12564	T12566	punct	+,mice
R3621	T12565	T12564	punct	/,+
R3622	T12566	T12562	pobj	mice,in
R3623	T12567	T12564	cc	or,+
R3624	T12568	T12569	punct	+,-
R3625	T12569	T12564	conj	-,+
R3626	T12570	T12569	punct	/,-
R3627	T12571	T12542	punct	.,were
R3628	T12573	T12574	det	The,levels
R3629	T12574	T12575	nsubj	levels,were
R3630	T12576	T12574	prep	of,levels
R3631	T12577	T12578	det	these,acids
R3632	T12578	T12576	pobj	acids,of
R3633	T12579	T12578	compound	amino,acids
R3634	T12580	T12574	prep	in,levels
R3635	T12581	T12582	det	the,mice
R3636	T12582	T12580	pobj	mice,in
R3637	T12583	T12584	punct	+,-
R3638	T12584	T12582	punct	-,mice
R3639	T12585	T12584	punct	/,-
R3640	T12586	T12575	acomp	comparable,were
R3641	T12587	T12586	prep	to,comparable
R3642	T12588	T12587	pobj	those,to
R3643	T12589	T12588	prep	in,those
R3644	T12590	T12591	punct	+,+
R3645	T12591	T12593	punct	+,mice
R3646	T12592	T12591	punct	/,+
R3647	T12593	T12589	pobj	mice,in
R3648	T12594	T12595	punct	(,Table
R3649	T12595	T12575	parataxis	Table,were
R3650	T12596	T12595	nummod	1,Table
R3651	T12597	T12595	punct	),Table
R3652	T12598	T12575	punct	.,were
R3653	T12600	T12601	prep	Because,suggested
R3654	T12602	T12600	pcomp	of,Because
R3655	T12603	T12604	det	the,decrease
R3656	T12604	T12600	pobj	decrease,Because
R3657	T12605	T12604	amod	abnormal,decrease
R3658	T12606	T12604	prep	in,decrease
R3659	T12607	T12608	det	the,level
R3660	T12608	T12606	pobj	level,in
R3661	T12609	T12608	compound	blood,level
R3662	T12610	T12608	compound	alanine,level
R3663	T12611	T12604	cc	and,decrease
R3664	T12612	T12613	amod	marked,rise
R3665	T12613	T12604	conj	rise,decrease
R3666	T12614	T12613	prep	in,rise
R3667	T12615	T12616	compound	blood,levels
R3668	T12616	T12614	pobj	levels,in
R3669	T12617	T12616	compound	BCAA,levels
R3670	T12618	T12619	dep	that,are
R3671	T12619	T12604	relcl	are,decrease
R3672	T12620	T12619	acomp	characteristic,are
R3673	T12621	T12620	prep	of,characteristic
R3674	T12622	T12621	pobj	MSUD,of
R3675	T12623	T12601	punct	", ",suggested
R3676	T12624	T12625	det	a,report
R3677	T12625	T12601	nsubj	report,suggested
R3678	T12626	T12625	amod	recent,report
R3679	T12627	T12625	prep	on,report
R3680	T12628	T12629	compound	MSUD,patients
R3681	T12629	T12627	pobj	patients,on
R3682	T12630	T12601	aux	has,suggested
R3683	T12631	T12632	mark	that,provides
R3684	T12632	T12601	ccomp	provides,suggested
R3685	T12633	T12634	det	the,ratio
R3686	T12634	T12632	nsubj	ratio,provides
R3687	T12635	T12634	prep	of,ratio
R3688	T12636	T12637	compound	BCAA,alanine
R3689	T12637	T12635	pobj	alanine,of
R3690	T12638	T12637	punct	/,alanine
R3691	T12639	T12640	det	a,measure
R3692	T12640	T12632	dobj	measure,provides
R3693	T12641	T12642	advmod	more,sensitive
R3694	T12642	T12640	amod	sensitive,measure
R3695	T12643	T12640	prep	of,measure
R3696	T12644	T12645	det	the,biochemistry
R3697	T12645	T12643	pobj	biochemistry,of
R3698	T12646	T12645	amod	abnormal,biochemistry
R3699	T12647	T12645	prep	of,biochemistry
R3700	T12648	T12647	pobj	MSUD,of
R3701	T12649	T12640	prep	than,measure
R3702	T12650	T12651	compound	BCAA,level
R3703	T12651	T12649	pobj	level,than
R3704	T12652	T12651	advmod	alone,level
R3705	T12653	T12654	punct	[,8
R3706	T12654	T12601	parataxis	8,suggested
R3707	T12655	T12654	punct	],8
R3708	T12656	T12601	punct	.,suggested
R3709	T12658	T12659	advmod	Therefore,expressed
R3710	T12660	T12659	punct	", ",expressed
R3711	T12661	T12659	nsubj	we,expressed
R3712	T12662	T12659	advmod	also,expressed
R3713	T12663	T12664	det	the,results
R3714	T12664	T12659	dobj	results,expressed
R3715	T12665	T12666	compound	amino,acid
R3716	T12666	T12664	compound	acid,results
R3717	T12667	T12659	prep	as,expressed
R3718	T12668	T12669	compound	BCAA,alanine
R3719	T12669	T12671	compound	alanine,ratio
R3720	T12670	T12669	punct	/,alanine
R3748	T12700	T12701	punct	+,-
R3749	T12701	T12696	conj	-,+
R3750	T12702	T12701	punct	/,-
R3751	T12703	T12676	punct	.,was
R3752	T12705	T12706	det	These,results
R3753	T12706	T12710	nsubj	results,are
R3754	T12707	T12706	compound	blood,results
R3755	T12708	T12709	compound	amino,acid
R3756	T12709	T12706	compound	acid,results
R3757	T12711	T12710	acomp	consistent,are
R3758	T12712	T12711	prep	with,consistent
R3759	T12713	T12714	det	the,concentrations
R3760	T12714	T12712	pobj	concentrations,with
R3761	T12715	T12714	acl	seen,concentrations
R3762	T12716	T12715	prep	in,seen
R3763	T12717	T12716	pobj	patients,in
R3764	T12718	T12717	prep	with,patients
R3765	T12719	T12718	pobj	MSUD,with
R3766	T12720	T12721	punct	[,15
R3767	T12721	T12710	parataxis	15,are
R3768	T12722	T12721	nummod	1,15
R3769	T12723	T12721	punct	",",15
R3770	T12724	T12721	nummod	8,15
R3771	T12725	T12721	punct	",",15
R3772	T12726	T12721	punct	],15
R3773	T12727	T12710	punct	.,are
R3803	T12761	T12760	advmod	ultimately,result
R3804	T12762	T12760	prep	in,result
R3805	T12763	T12764	amod	neonatal,lethality
R3806	T12764	T12762	pobj	lethality,in
R3807	T12765	T12760	punct	.,result
R3808	T12767	T12768	det	These,phenotypes
R3809	T12768	T12769	nsubj	phenotypes,are
R3810	T12770	T12771	advmod	remarkably,similar
R3811	T12771	T12769	acomp	similar,are
R3812	T12772	T12771	prep	to,similar
R3813	T12773	T12772	pobj	that,to
R3814	T12774	T12773	acl	observed,that
R3815	T12775	T12774	prep	in,observed
R3816	T12776	T12775	pobj	humans,in
R3817	T12777	T12776	prep	with,humans
R3818	T12778	T12779	det	the,form
R3819	T12779	T12777	pobj	form,with
R3820	T12780	T12779	amod	classic,form
R3821	T12781	T12779	prep	of,form
R3822	T12782	T12781	pobj	MSUD,of
R3823	T12783	T12769	punct	.,are
R3824	T12785	T12786	advmod	Thus,model
R3825	T12787	T12786	punct	", ",model
R3826	T12788	T12789	compound	E2,mice
R3827	T12789	T12786	nsubj	mice,model
R3828	T12790	T12789	compound	knockout,mice
R3829	T12791	T12786	advmod	closely,model
R3830	T12792	T12793	amod	classic,MSUD
R3831	T12793	T12786	dobj	MSUD,model
R3832	T12794	T12786	punct	.,model
R3835	T15726	T15727	compound	Knockout,mice
R3836	T15727	T15728	nsubj	mice,model
R3837	T15729	T15727	acl	expressing,mice
R3838	T15730	T15731	det	a,transgene
R3839	T15731	T15729	dobj	transgene,expressing
R3840	T15732	T15731	amod	human,transgene
R3841	T15733	T15731	compound	E2,transgene
R3842	T15734	T15735	det	a,form
R3843	T15735	T15728	dobj	form,model
R3844	T15736	T15735	amod	variant,form
R3845	T15737	T15735	prep	of,form
R3846	T15738	T15737	pobj	MSUD,of
R3847	T15739	T15740	dep	that,mimics
R3848	T15740	T15735	relcl	mimics,form
R3849	T15741	T15742	amod	intermediate,MSUD
R3850	T15742	T15740	dobj	MSUD,mimics
R3851	T15744	T15745	aux	To,create
R3852	T15745	T15746	advcl	create,used
R3853	T15747	T15748	det	a,model
R3854	T15748	T15745	dobj	model,create
R3855	T15749	T15748	amod	murine,model
R3856	T15750	T15748	prep	of,model
R3857	T15751	T15752	det	the,form
R3858	T15752	T15750	pobj	form,of
R3859	T15753	T15752	amod	intermediate,form
R3860	T15754	T15752	compound	variant,form
R3861	T15755	T15752	prep	of,form
R3862	T15756	T15755	pobj	MSUD,of
R3863	T15757	T15746	punct	", ",used
R3864	T15758	T15746	nsubj	we,used
R3865	T15759	T15760	det	a,strategy
R3866	T15760	T15746	dobj	strategy,used
R3867	T15761	T15760	amod	transgenic,strategy
R3868	T15762	T15763	aux	to,rescue
R3869	T15763	T15746	advcl	rescue,used
R3870	T15764	T15765	det	the,elevation
R3871	T15765	T15763	dobj	elevation,rescue
R3872	T15766	T15765	amod	severe,elevation
R3873	T15767	T15765	prep	of,elevation
R3874	T15768	T15767	pobj	BCAA,of
R3875	T15769	T15765	cc	and,elevation
R3876	T15770	T15771	amod	neonatal,lethality
R3877	T15771	T15765	conj	lethality,elevation
R3878	T15772	T15773	dep	that,occurs
R3879	T15773	T15771	relcl	occurs,lethality
R3880	T15774	T15773	prep	in,occurs
R3881	T15775	T15776	det	the,model
R3882	T15776	T15774	pobj	model,in
R3883	T15777	T15776	amod	classic,model
R3884	T15778	T15776	compound	MSUD,model
R3885	T15779	T15776	compound	mouse,model
R3886	T15780	T15746	punct	.,used
R3887	T15782	T15783	poss	Our,strategy
R3888	T15783	T15784	nsubjpass	strategy,composed
R3889	T15785	T15784	auxpass	was,composed
R3890	T15786	T15784	prep	of,composed
R3891	T15787	T15788	det	a,system
R3892	T15788	T15786	pobj	system,of
R3893	T15789	T15790	nummod	two,part
R3894	T15790	T15788	nmod	part,system
R3895	T15791	T15788	amod	transgenic,system
R3896	T15792	T15793	aux	to,express
R3897	T15793	T15788	advcl	express,system
R3898	T15794	T15795	amod	human,E2
R3899	T15795	T15793	dobj	E2,express
R3900	T15796	T15793	prep	in,express
R3901	T15797	T15796	pobj	liver,in
R3902	T15798	T15793	prep	on,express
R3903	T15799	T15800	det	the,background
R3904	T15800	T15798	pobj	background,on
R3905	T15801	T15802	compound	E2,knockout
R3906	T15802	T15800	compound	knockout,background
R3907	T15803	T15784	punct	.,composed
R3908	T15805	T15806	det	This,system
R3909	T15806	T15808	nsubj	system,consisted
R3910	T15807	T15806	amod	bi-transgenic,system
R3911	T15809	T15808	prep	of,consisted
R3912	T15810	T15811	det	a,transgene
R3913	T15811	T15809	pobj	transgene,of
R3914	T15812	T15813	compound	LAP,tTA
R3915	T15813	T15811	compound	tTA,transgene
R3916	T15814	T15813	punct	-,tTA
R3917	T15815	T15811	cc	and,transgene
R3918	T15816	T15817	det	a,transgene
R3919	T15817	T15811	conj	transgene,transgene
R3920	T15818	T15819	compound	TRE,E2
R3921	T15819	T15817	compound	E2,transgene
R3922	T15820	T15819	punct	-,E2
R3923	T15821	T15822	punct	(,3A
R3924	T15822	T15808	parataxis	3A,consisted
R3925	T15823	T15822	compound	Fig.,3A
R3926	T15824	T15822	punct	),3A
R3927	T15825	T15808	punct	.,consisted
R3944	T15844	T15842	pobj	transactivator,of
R3945	T15845	T15846	npadvmod	tetracycline,controlled
R3946	T15846	T15844	amod	controlled,transactivator
R3947	T15847	T15846	punct	-,controlled
R3948	T15848	T15844	punct	(,transactivator
R3949	T15849	T15844	appos	tTA,transactivator
R3950	T15850	T15844	punct	),transactivator
R3951	T15851	T15844	punct	", ",transactivator
R3952	T15852	T15853	det	a,factor
R3953	T15853	T15844	appos	factor,transactivator
R3954	T15854	T15853	compound	transcription,factor
R3955	T15855	T15856	dep	that,stimulates
R3956	T15856	T15853	relcl	stimulates,factor
R3957	T15857	T15856	dobj	expression,stimulates
R3958	T15858	T15857	prep	of,expression
R3959	T15859	T15858	pobj	promoters,of
R3960	T15860	T15861	dep	that,harbor
R3961	T15861	T15859	relcl	harbor,promoters
R3962	T15862	T15863	det	a,element
R3963	T15863	T15861	dobj	element,harbor
R3964	T15864	T15863	compound	transactivator,element
R3965	T15865	T15863	compound	response,element
R3966	T15866	T15863	punct	(,element
R3967	T15867	T15863	appos	TRE,element
R3968	T15868	T15832	punct	),directs
R3969	T15869	T15832	punct	.,directs
R3970	T15871	T15872	det	The,transgene
R3971	T15872	T15876	nsubjpass	transgene,designed
R3972	T15873	T15874	compound	TRE,E2
R3973	T15874	T15872	compound	E2,transgene
R3974	T15875	T15874	punct	-,E2
R3975	T15877	T15876	auxpass	was,designed
R3976	T15878	T15879	aux	to,express
R3977	T15879	T15876	advcl	express,designed
R3978	T15880	T15881	det	a,cDNA
R3979	T15881	T15879	dobj	cDNA,express
R3980	T15882	T15881	amod	human,cDNA
R3981	T15883	T15881	compound	E2,cDNA
R3982	T15884	T15879	prep	from,express
R3983	T15885	T15886	det	a,TRE
R3984	T15886	T15884	pobj	TRE,from
R3985	T15887	T15886	acl	containing,TRE
R3986	T15888	T15889	amod	minimal,promoter
R3987	T15889	T15887	dobj	promoter,containing
R3988	T15890	T15879	prep	upon,express
R3989	T15891	T15890	pobj	stimulation,upon
R3990	T15892	T15891	prep	by,stimulation
R3991	T15893	T15892	pobj	tTA,by
R3992	T15894	T15876	punct	.,designed
R4008	T15941	T15942	punct	[,34
R4009	T15942	T15936	parataxis	34,zed
R4010	T15943	T15942	punct	],34
R4011	T15946	T15947	amod	Pronuclear,microinjection
R4012	T15947	T15948	nsubjpass	microinjection,used
R4013	T15949	T15948	auxpass	was,used
R4014	T15950	T15951	aux	to,produce
R4015	T15951	T15948	advcl	produce,used
R4016	T15952	T15953	amod	transgenic,mice
R4017	T15953	T15951	dobj	mice,produce
R4018	T15954	T15955	dep	that,harbored
R4019	T15955	T15953	relcl	harbored,mice
R4020	T15956	T15957	det	the,transgene
R4021	T15957	T15955	dobj	transgene,harbored
R4022	T15958	T15959	compound	TRE,E2
R4023	T15959	T15957	compound	E2,transgene
R4024	T15960	T15959	punct	-,E2
R4025	T15961	T15948	punct	.,used
R4026	T15963	T15964	prep	From,identified
R4027	T15965	T15963	pobj	injections,From
R4028	T15966	T15965	prep	at,injections
R4029	T15967	T15968	det	the,University
R4030	T15968	T15966	pobj	University,at
R4031	T15969	T15968	prep	of,University
R4032	T15970	T15969	pobj	Pittsburgh,of
R4033	T15971	T15964	punct	", ",identified
R4034	T15972	T15973	nummod	2,founders
R4035	T15973	T15964	nsubjpass	founders,identified
R4036	T15974	T15975	npadvmod	transgene,positive
R4037	T15975	T15973	amod	positive,founders
R4038	T15976	T15964	auxpass	were,identified
R4039	T15977	T15978	dep	that,led
R4040	T15978	T15964	ccomp	led,identified
R4041	T15979	T15978	prep	to,led
R4042	T15980	T15981	det	the,generation
R4043	T15981	T15979	pobj	generation,to
R4044	T15982	T15981	prep	of,generation
R4045	T15983	T15984	nummod	3,lines
R4046	T15984	T15982	pobj	lines,of
R4047	T15985	T15984	amod	different,lines
R4048	T15986	T15984	amod	transgenic,lines
R4049	T15987	T15988	punct	(,A
R4050	T15988	T15984	parataxis	A,lines
R4051	T15989	T15988	compound	Lines,A
R4052	T15990	T15988	punct	", ",A
R4053	T15991	T15988	conj	B,A
R4054	T15992	T15991	punct	", ",B
R4055	T15993	T15991	cc	&,B
R4056	T15994	T15991	conj	D,B
R4057	T15995	T15988	punct	),A
R4058	T15996	T15964	punct	.,identified
R4059	T15998	T15999	prep	From,obtained
R4060	T16000	T16001	det	the,injections
R4061	T16001	T15998	pobj	injections,From
R4062	T16002	T16001	prep	at,injections
R4063	T16003	T16004	det	the,University
R4064	T16004	T16002	pobj	University,at
R4065	T16005	T16004	prep	of,University
R4066	T16006	T16005	pobj	Cincinnati,of
R4067	T16007	T15999	punct	", ",obtained
R4068	T16008	T15999	nsubj	we,obtained
R4069	T16009	T16010	nummod	8,founders
R4070	T16010	T15999	dobj	founders,obtained
R4071	T16011	T16012	npadvmod	transgene,positive
R4072	T16012	T16010	amod	positive,founders
R4073	T16013	T15999	punct	.,obtained
R4074	T16015	T16016	amod	Subsequent,breeding
R4075	T16016	T16017	nsubj	breeding,revealed
R4076	T16018	T16016	prep	of,breeding
R4077	T16019	T16020	det	these,founders
R4078	T16020	T16018	pobj	founders,of
R4079	T16021	T16022	mark	that,had
R4080	T16022	T16017	ccomp	had,revealed
R4081	T16023	T16022	nsubj	many,had
R4082	T16024	T16023	prep	of,many
R4083	T16025	T16026	det	the,animals
R4084	T16026	T16024	pobj	animals,of
R4085	T16027	T16028	amod	multiple,sites
R4086	T16028	T16022	dobj	sites,had
R4087	T16029	T16028	compound	transgene,sites
R4088	T16030	T16028	compound	insertion,sites
R4089	T16031	T16032	dep	that,segregated
R4090	T16032	T16028	relcl	segregated,sites
R4091	T16033	T16017	punct	.,revealed
R4092	T16035	T16036	nsubj	We,established
R4093	T16037	T16038	det	a,total
R4094	T16038	T16036	dobj	total,established
R4095	T16039	T16038	prep	of,total
R4096	T16040	T16041	nummod	15,lines
R4097	T16041	T16039	pobj	lines,of
R4098	T16042	T16041	amod	different,lines
R4099	T16043	T16041	amod	transgenic,lines
R4100	T16044	T16036	prep	from,established
R4101	T16045	T16046	det	these,founders
R4102	T16046	T16044	pobj	founders,from
R4103	T16047	T16036	punct	.,established
R4104	T16049	T16050	amod	Limited,resources
R4105	T16050	T16051	nsubj	resources,allowed
R4106	T16052	T16053	nsubj	us,focus
R4107	T16053	T16051	ccomp	focus,allowed
R4108	T16054	T16053	aux	to,focus
R4109	T16055	T16053	advmod	only,focus
R4110	T16056	T16053	prep	on,focus
R4111	T16057	T16058	det	a,total
R4112	T16058	T16056	pobj	total,on
R4113	T16059	T16058	prep	of,total
R4114	T16060	T16059	pobj	9,of
R4115	T16061	T16060	prep	of,9
R4116	T16062	T16063	det	these,lines
R4117	T16063	T16061	pobj	lines,of
R4118	T16064	T16051	punct	.,allowed
R4119	T16066	T16067	det	These,lines
R4120	T16067	T16068	nsubj	lines,differed
R4121	T16069	T16068	advmod	substantially,differed
R4122	T16070	T16068	prep	in,differed
R4123	T16071	T16072	compound	transgene,number
R4124	T16072	T16070	pobj	number,in
R4125	T16073	T16072	compound	copy,number
R4126	T16074	T16075	mark	as,compared
R4127	T16075	T16068	advcl	compared,differed
R4128	T16076	T16075	prep	by,compared
R4129	T16077	T16078	compound	Southern,blot
R4130	T16078	T16079	compound	blot,analysis
R4131	T16079	T16076	pobj	analysis,by
R4132	T16080	T16079	prep	of,analysis
R4133	T16081	T16082	compound	tail,DNA
R4134	T16082	T16080	pobj	DNA,of
R4135	T16083	T16084	punct	(,shown
R4136	T16084	T16068	parataxis	shown,differed
R4137	T16085	T16084	nsubj	data,shown
R4138	T16086	T16084	neg	not,shown
R4139	T16087	T16084	punct	),shown
R4140	T16088	T16068	punct	.,differed
R4141	T16090	T16091	amod	Transgenic,mice
R4142	T16091	T16095	nsubjpass	mice,crossed
R4143	T16092	T16093	compound	TRE,E2
R4144	T16093	T16091	compound	E2,mice
R4145	T16094	T16093	punct	-,E2
R4146	T16096	T16091	prep	from,mice
R4147	T16097	T16098	det	each,line
R4148	T16098	T16096	pobj	line,from
R4149	T16099	T16100	punct	(,offspring
R4150	T16100	T16098	parataxis	offspring,line
R4151	T16101	T16100	preconj	either,offspring
R4152	T16102	T16100	nmod	founders,offspring
R4153	T16103	T16102	cc	or,founders
R4154	T16104	T16102	conj	F1,founders
R4155	T16105	T16100	punct	),offspring
R4156	T16106	T16095	auxpass	were,crossed
R4157	T16107	T16095	prep	to,crossed
R4158	T16108	T16107	pobj	mice,to
R4159	T16109	T16110	dep	that,were
R4160	T16110	T16108	relcl	were,mice
R4161	T16111	T16110	acomp	positive,were
R4162	T16112	T16111	prep	for,positive
R4163	T16113	T16114	det	the,transgene
R4164	T16114	T16112	pobj	transgene,for
R4165	T16115	T16116	compound	LAP,tTA
R4166	T16116	T16114	compound	tTA,transgene
R4167	T16117	T16116	punct	-,tTA
R4168	T16118	T16110	cc	and,were
R4169	T16119	T16110	conj	were,were
R4170	T16120	T16119	acomp	heterozygous,were
R4171	T16121	T16120	prep	for,heterozygous
R4172	T16122	T16123	det	the,knockout
R4173	T16123	T16121	pobj	knockout,for
R4174	T16124	T16123	compound	E2,knockout
R4175	T16125	T16095	punct	.,crossed
R4176	T16127	T16128	advmod	Ultimately,used
R4177	T16129	T16128	punct	", ",used
R4178	T16130	T16131	amod	breeding,pairs
R4179	T16131	T16128	nsubjpass	pairs,used
R4180	T16132	T16128	auxpass	were,used
R4181	T16133	T16134	prep	in,were
R4182	T16134	T16128	ccomp	were,used
R4183	T16135	T16133	pobj	which,in
R4184	T16136	T16137	det	the,mice
R4185	T16137	T16134	nsubj	mice,were
R4186	T16138	T16134	acomp	heterozygous,were
R4187	T16139	T16138	prep	for,heterozygous
R4188	T16140	T16141	det	the,transgene
R4189	T16141	T16139	pobj	transgene,for
R4190	T16142	T16143	compound	LAP,tTA
R4191	T16143	T16141	compound	tTA,transgene
R4192	T16144	T16143	punct	-,tTA
R4193	T16145	T16141	punct	", ",transgene
R4194	T16146	T16147	det	the,transgene
R4195	T16147	T16141	conj	transgene,transgene
R4196	T16148	T16149	compound	TRE,E2
R4197	T16149	T16147	compound	E2,transgene
R4198	T16150	T16149	punct	-,E2
R4199	T16151	T16147	punct	", ",transgene
R4200	T16152	T16147	cc	and,transgene
R4201	T16153	T16154	det	the,knockout
R4202	T16154	T16147	conj	knockout,transgene
R4203	T16155	T16154	compound	E2,knockout
R4204	T16156	T16128	punct	.,used
R4205	T16158	T16159	aux	To,screen
R4206	T16159	T16161	advcl	screen,genotyped
R4207	T16160	T16159	advmod	efficiently,screen
R4208	T16162	T16159	prep	for,screen
R4209	T16163	T16164	det	the,ability
R4210	T16164	T16162	pobj	ability,for
R4211	T16165	T16164	prep	of,ability
R4212	T16166	T16167	det	the,transgenes
R4213	T16167	T16165	pobj	transgenes,of
R4214	T16168	T16169	aux	to,rescue
R4215	T16169	T16164	acl	rescue,ability
R4216	T16170	T16171	det	the,knockout
R4217	T16171	T16169	dobj	knockout,rescue
R4218	T16172	T16169	prep	from,rescue
R4219	T16173	T16174	amod	neonatal,lethality
R4220	T16174	T16172	pobj	lethality,from
R4221	T16175	T16161	punct	", ",genotyped
R4222	T16176	T16161	nsubj	we,genotyped
R4223	T16177	T16161	dobj	litters,genotyped
R4224	T16178	T16161	prep	at,genotyped
R4225	T16179	T16178	pobj	weaning,at
R4226	T16180	T16161	punct	.,genotyped
R4227	T16182	T16183	det	This,strategy
R4228	T16183	T16185	nsubjpass	strategy,expected
R4229	T16184	T16183	amod	breeding,strategy
R4230	T16186	T16185	auxpass	is,expected
R4231	T16187	T16188	aux	to,result
R4232	T16188	T16185	xcomp	result,expected
R4233	T16189	T16188	prep	in,result
R4234	T16190	T16191	det	a,maximum
R4235	T16191	T16189	pobj	maximum,in
R4236	T16192	T16191	amod	theoretical,maximum
R4237	T16193	T16191	prep	of,maximum
R4238	T16194	T16193	pobj	animals,of
R4239	T16195	T16194	prep	with,animals
R4240	T16196	T16197	det	the,genotype
R4241	T16197	T16195	pobj	genotype,with
R4242	T16198	T16197	compound	rescue,genotype
R4243	T16199	T16200	punct	(,knockout
R4244	T16200	T16197	parataxis	knockout,genotype
R4245	T16201	T16200	advmod	i.e.,knockout
R4246	T16202	T16200	punct	", ",knockout
R4247	T16203	T16200	amod	homozygous,knockout
R4248	T16204	T16200	compound	E2,knockout
R4249	T16205	T16200	cc	and,knockout
R4250	T16206	T16200	conj	positive,knockout
R4251	T16207	T16206	prep	for,positive
R4252	T16208	T16209	det	both,transgenes
R4253	T16209	T16207	pobj	transgenes,for
R4254	T16210	T16200	punct	),knockout
R4255	T16211	T16191	prep	of,maximum
R4256	T16212	T16213	nummod	14,%
R4257	T16213	T16211	pobj	%,of
R4258	T16214	T16185	punct	.,expected
R4259	T16216	T16217	compound	Fig.,4A
R4260	T16217	T16218	nsubj	4A,shows
R4261	T16219	T16220	det	the,percentage
R4262	T16220	T16218	dobj	percentage,shows
R4263	T16221	T16220	prep	of,percentage
R4264	T16222	T16221	pobj	mice,of
R4265	T16223	T16222	amod	alive,mice
R4266	T16224	T16223	prep	at,alive
R4267	T16225	T16224	pobj	weaning,at
R4268	T16226	T16220	prep	with,percentage
R4269	T16227	T16228	det	the,genotype
R4270	T16228	T16226	pobj	genotype,with
R4271	T16229	T16228	compound	rescue,genotype
R4272	T16230	T16228	prep	from,genotype
R4273	T16231	T16232	det	each,line
R4274	T16232	T16230	pobj	line,from
R4275	T16279	T16280	advmod	Thus,appears
R4276	T16233	T16232	amod	transgenic,line
R4277	T16281	T16280	punct	", ",appears
R4278	T16234	T16232	acl	tested,line
R4279	T16282	T16283	det	the,transgene
R4280	T16283	T16280	nsubj	transgene,appears
R4281	T16235	T16218	punct	.,shows
R4282	T16284	T16283	compound	525A,transgene
R4283	T16285	T16286	aux	to,be
R4284	T16237	T16238	amod	Considerable,variability
R4285	T16286	T16280	xcomp	be,appears
R4286	T16287	T16288	advmod	highly,effective
R4287	T16288	T16286	acomp	effective,be
R4288	T16289	T16288	prep	at,effective
R4289	T16238	T16239	nsubjpass	variability,observed
R4290	T16240	T16239	auxpass	was,observed
R4293	T16241	T16239	prep	between,observed
R4297	T16242	T16241	pobj	lines,between
R4302	T16243	T16239	punct	.,observed
R4305	T16245	T16246	det	The,line
R4309	T16246	T16247	nsubj	line,was
R4311	T16248	T16246	prep	with,line
R4316	T16249	T16250	det	the,percentage
R4318	T16250	T16248	pobj	percentage,with
R4322	T16251	T16250	amod	highest,percentage
R4326	T16252	T16250	prep	of,percentage
R4328	T16253	T16254	compound	rescue,mice
R4332	T16254	T16252	pobj	mice,of
R4336	T16255	T16250	prep	at,percentage
R4340	T16256	T16255	pobj	weaning,at
R4344	T16257	T16258	nmod	line,A
R4345	T16333	T16334	amod	weaned,pups
R4346	T16334	T16332	pobj	pups,of
R4347	T16335	T16319	punct	.,produced
R4348	T16258	T16247	attr	A,was
R4349	T16259	T16258	nummod	525,A
R4350	T16260	T16247	punct	.,was
R4351	T16262	T16263	advmod	Approximately,10
R4352	T16263	T16264	nummod	10,%
R4354	T16264	T16265	nsubj	%,had
R4355	T16266	T16264	prep	of,%
R4356	T16267	T16268	amod	weaned,pups
R4357	T16268	T16266	pobj	pups,of
R4358	T16269	T16268	punct	", ",pups
R4359	T16270	T16268	amod	surviving,pups
R4362	T16271	T16264	prep	from,%
R4363	T16272	T16273	det	this,line
R4364	T16273	T16271	pobj	line,from
R4365	T16274	T16275	det	the,genotype
R4366	T16275	T16265	dobj	genotype,had
R4367	T16276	T16275	compound	rescue,genotype
R4368	T16277	T16265	punct	.,had
R4406	T16399	T16382	punct	.,shows
R4410	T16401	T16402	det	The,values
R4412	T16402	T16406	nsubj	values,were
R4413	T16403	T16404	compound	BCAA,alanine
R4414	T16404	T16402	compound	alanine,values
R4416	T16405	T16404	punct	/,alanine
R4420	T16407	T16402	prep	for,values
R4424	T16408	T16407	pobj	mice,for
R4428	T16409	T16408	prep	from,mice
R4432	T16410	T16411	det	both,lines
R4436	T16411	T16409	pobj	lines,from
R4439	T16521	T16520	compound	E2,protein
R4440	T16412	T16413	advmod	significantly,elevated
R4441	T16522	T16514	prep	in,activity
R4442	T16523	T16522	pobj	liver,in
R4443	T16524	T16523	prep	of,liver
R4444	T16413	T16406	acomp	elevated,were
R4445	T16525	T16526	compound	Lines,A
R4446	T16526	T16524	pobj	A,of
R4447	T16527	T16526	cc	and,A
R4448	T16414	T16406	prep	compared,were
R4449	T16528	T16526	conj	525A,A
R4450	T16529	T16503	auxpass	was,examined
R4451	T16415	T16414	prep	to,compared
R4452	T16530	T16503	punct	.,examined
R4453	T16416	T16415	pobj	controls,to
R4454	T16417	T16416	prep	for,controls
R4455	T16532	T16533	nmod	BCKDH,activity
R4456	T16533	T16535	nsubj	activity,was
R4457	T16534	T16533	amod	enzymatic,activity
R4458	T16418	T16417	pobj	all,for
R4459	T16536	T16533	prep	in,activity
R4460	T16537	T16536	pobj	liver,in
R4461	T16538	T16537	prep	from,liver
R4462	T16539	T16540	compound	Lines,A
R4463	T16419	T16418	prep	of,all
R4464	T16540	T16538	pobj	A,from
R4465	T16541	T16540	cc	and,A
R4466	T16420	T16421	det	the,points
R4467	T16542	T16540	conj	525A,A
R4468	T16543	T16544	punct	~,6
R4469	T16544	T16545	nummod	6,%
R4470	T16421	T16419	pobj	points,of
R4471	T16545	T16535	attr	%,was
R4472	T16546	T16544	cc	and,6
R4473	T16422	T16421	compound	time,points
R4474	T16547	T16544	conj	5,6
R4475	T16548	T16535	punct	", ",was
R4476	T16549	T16535	advmod	respectively,was
R4477	T16423	T16421	acl	analyzed,points
R4478	T16550	T16535	punct	", ",was
R4479	T16551	T16535	prep	of,was
R4480	T16552	T16553	det	the,activity
R4481	T16424	T16406	punct	.,were
R4482	T16553	T16551	pobj	activity,of
R4483	T16554	T16553	amod	enzymatic,activity
R4484	T16555	T16553	amod	present,activity
R4485	T16427	T16428	mark	that,are
R4486	T16556	T16555	prep	in,present
R4487	T16557	T16558	compound	control,liver
R4488	T16558	T16556	pobj	liver,in
R4489	T16559	T16560	punct	(,4C
R4490	T16560	T16535	parataxis	4C,was
R4491	T16428	T16426	ccomp	are,Note
R4492	T16561	T16560	compound	Fig.,4C
R4493	T16562	T16560	punct	),4C
R4494	T16563	T16535	punct	.,was
R4495	T16429	T16430	det	the,values
R4496	T16565	T16566	mark	As,shown
R4497	T16430	T16428	nsubj	values,are
R4498	T16566	T16567	advcl	shown,was
R4499	T16568	T16566	prep	in,shown
R4500	T16431	T16432	compound	BCAA,alanine
R4501	T16569	T16570	compound	Fig.,3B
R4502	T16570	T16568	pobj	3B,in
R4503	T16571	T16567	punct	", ",was
R4504	T16432	T16430	compound	alanine,values
R4505	T16572	T16573	det	the,amount
R4506	T16573	T16567	nsubj	amount,was
R4507	T16574	T16573	prep	of,amount
R4508	T16575	T16576	amod	human,E2
R4509	T16576	T16574	pobj	E2,of
R4510	T16433	T16432	punct	/,alanine
R4511	T16577	T16578	punct	(,Kd
R4512	T16578	T16576	parataxis	Kd,E2
R4513	T16579	T16580	amod	predicted,MW
R4514	T16580	T16578	nsubj	MW,Kd
R4515	T16434	T16430	prep	for,values
R4516	T16581	T16582	punct	~,54
R4517	T16582	T16578	nummod	54,Kd
R4518	T16583	T16578	punct	),Kd
R4519	T16435	T16436	det	the,mice
R4520	T16584	T16573	prep	in,amount
R4521	T16585	T16586	det	these,mice
R4522	T16586	T16584	pobj	mice,in
R4523	T16436	T16434	pobj	mice,for
R4524	T16587	T16586	amod	transgenic,mice
R4525	T16588	T16589	advmod	quite,variable
R4526	T16589	T16567	acomp	variable,was
R4527	T16437	T16436	amod	transgenic,mice
R4528	T16590	T16589	prep	between,variable
R4529	T16438	T16428	acomp	intermediate,are
R4530	T16439	T16428	prep	between,are
R4531	T16591	T16590	pobj	mice,between
R4532	T16592	T16567	punct	.,was
R4534	T16594	T16595	prep	In,was
R4535	T16596	T16594	pobj	some,In
R4536	T16597	T16596	prep	of,some
R4538	T16598	T16599	det	these,mice
R4539	T16599	T16597	pobj	mice,of
R4541	T16600	T16599	amod	transgenic,mice
R4542	T16601	T16595	punct	", ",was
R4543	T16602	T16603	det	the,level
R4545	T16603	T16595	nsubj	level,was
R4546	T16604	T16603	prep	of,level
R4547	T16605	T16606	amod	human,E2
R4549	T16606	T16604	pobj	E2,of
R4550	T16607	T16608	advmod	approximately,equal
R4554	T16608	T16595	acomp	equal,was
R4555	T16609	T16608	prep	to,equal
R4557	T16610	T16611	det	the,amount
R4558	T16611	T16609	pobj	amount,to
R4559	T16612	T16611	prep	of,amount
R4560	T16613	T16614	compound	mouse,E2
R4561	T16614	T16612	pobj	E2,of
R4562	T16615	T16616	punct	(,Kd
R4564	T16616	T16614	parataxis	Kd,E2
R4566	T16617	T16618	punct	~,47
R4567	T16618	T16616	nummod	47,Kd
R4569	T16619	T16616	punct	),Kd
R4570	T16620	T16611	acl	produced,amount
R4571	T16621	T16620	prep	in,produced
R4572	T16622	T16621	pobj	liver,in
R4573	T16623	T16622	prep	of,liver
R4575	T16624	T16625	amod	nontransgenic,mice
R4576	T16625	T16623	pobj	mice,of
R4578	T16626	T16625	compound	control,mice
R4579	T16627	T16595	punct	.,was
R4581	T16629	T16630	det	The,observations
R4582	T16630	T16631	nsubj	observations,suggest
R4584	T16632	T16633	mark	that,result
R4585	T16633	T16630	acl	result,observations
R4587	T16634	T16635	det	these,amounts
R4588	T16635	T16633	nsubj	amounts,result
R4589	T16636	T16637	advmod	near,normal
R4591	T16637	T16635	amod	normal,amounts
R4592	T16638	T16635	prep	of,amounts
R4594	T16639	T16640	compound	E2,protein
R4595	T16640	T16638	pobj	protein,of
R4596	T16641	T16633	prep	in,result
R4598	T16642	T16643	advmod	only,6
R4599	T16643	T16647	nummod	6,%
R4600	T16644	T16643	punct	~,6
R4602	T16645	T16643	quantmod	5,6
R4603	T16646	T16643	punct	–,6
R4604	T16647	T16641	pobj	%,in
R4606	T16648	T16647	prep	of,%
R4607	T16649	T16650	amod	normal,activity
R4608	T16650	T16648	pobj	activity,of
R4610	T16651	T16650	compound	BCKDH,activity
R4611	T16652	T16650	compound	enzyme,activity
R4612	T16653	T16654	mark	that,functioning
R4613	T16654	T16631	ccomp	functioning,suggest
R4614	T16655	T16656	nmod	transgene,E2
R4615	T16656	T16654	nsubj	E2,functioning
R4617	T16657	T16656	amod	derived,E2
R4618	T16658	T16654	aux	is,functioning
R4619	T16659	T16654	prep	at,functioning
R4621	T16660	T16661	det	a,level
R4622	T16661	T16659	pobj	level,at
R4624	T16662	T16661	amod	suboptimal,level
R4625	T16663	T16631	punct	.,suggest
R4627	T16665	T16666	nsubj	It,is
R4628	T16667	T16666	acomp	probable,is
R4630	T16668	T16669	mark	that,interfered
R4631	T16669	T16666	ccomp	interfered,is
R4632	T16670	T16671	det	the,tag
R4634	T16671	T16669	nsubj	tag,interfered
R4635	T16672	T16673	compound	c,myc
R4637	T16673	T16671	compound	myc,tag
R4638	T16674	T16673	punct	-,myc
R4639	T16675	T16671	prep	at,tag
R4641	T16676	T16677	det	the,terminus
R4642	T16677	T16675	pobj	terminus,at
R4643	T16678	T16677	compound	carboxy,terminus
R4645	T16679	T16677	prep	of,terminus
R4646	T16680	T16681	det	the,E2
R4647	T16681	T16679	pobj	E2,of
R4649	T16682	T16683	npadvmod	transgene,derived
R4650	T16683	T16681	amod	derived,E2
R4651	T16684	T16681	amod	human,E2
R4653	T16685	T16669	prep	with,interfered
R4654	T16686	T16687	amod	enzymatic,activity
R4655	T16687	T16685	pobj	activity,with
R4657	T16688	T16666	punct	.,is
R4659	T16690	T16691	det	This,interpretation
R4660	T16691	T16692	nsubj	interpretation,is
R4662	T16693	T16692	acomp	consistent,is
R4663	T16694	T16693	prep	with,consistent
R4664	T16695	T16696	amod	previous,studies
R4665	T16696	T16694	pobj	studies,with
R4666	T16697	T16698	dep	which,revealed
R4668	T16698	T16696	relcl	revealed,studies
R4669	T16699	T16698	aux	have,revealed
R4670	T16700	T16701	mark	that,is
R4673	T16701	T16698	ccomp	is,revealed
R4674	T16702	T16703	det	the,terminus
R4675	T16714	T16701	acomp	essential,is
R4676	T16703	T16701	nsubj	terminus,is
R4677	T16704	T16703	compound	carboxy,terminus
R4678	T16705	T16703	prep	of,terminus
R4679	T16706	T16707	det	an,subunit
R4680	T16707	T16705	pobj	subunit,of
R4681	T16708	T16707	amod	analogous,subunit
R4682	T16715	T16714	prep	for,essential
R4683	T16709	T16707	prep	of,subunit
R4684	T16710	T16711	det	the,complex
R4685	T16711	T16709	pobj	complex,of
R4686	T16716	T16717	compound	subunit,interactions
R4687	T16712	T16711	compound	pyruvate,complex
R4688	T16713	T16711	compound	dehydrogenase,complex
R4689	T16717	T16715	pobj	interactions,for
R4690	T16718	T16719	punct	[,35
R4691	T16719	T16701	parataxis	35,is
R4692	T16820	T16819	pobj	E2,of
R4693	T16821	T16808	acomp	negligible,is
R4694	T16720	T16719	punct	],35
R4695	T16822	T16808	prep	in,is
R4696	T16823	T16824	det	those,tissues
R4697	T16824	T16822	pobj	tissues,in
R4698	T16721	T16701	cc	and,is
R4699	T16825	T16808	punct	.,is
R4700	T16722	T16723	nsubj	insertion,interfered
R4701	T16827	T16828	amod	Long,term
R4702	T16828	T16830	compound	term,survival
R4703	T16829	T16828	punct	-,term
R4704	T16723	T16701	conj	interfered,is
R4705	T16830	T16831	nsubjpass	survival,plotted
R4706	T16724	T16722	prep	of,insertion
R4707	T16832	T16830	prep	of,survival
R4708	T16833	T16834	det	the,mice
R4709	T16834	T16832	pobj	mice,of
R4710	T16725	T16726	det	a,tag
R4711	T16835	T16834	prep	from,mice
R4712	T16836	T16837	det	these,lines
R4713	T16837	T16835	pobj	lines,from
R4714	T16838	T16837	nummod	two,lines
R4715	T16839	T16837	amod	transgenic,lines
R4716	T16840	T16841	dep	that,survived
R4717	T16726	T16724	pobj	tag,of
R4718	T16841	T16837	relcl	survived,lines
R4719	T16842	T16841	prep	beyond,survived
R4720	T16843	T16842	pobj	weaning,beyond
R4721	T16727	T16726	compound	Hisx6,tag
R4722	T16844	T16831	auxpass	is,plotted
R4723	T16845	T16831	prep	in,plotted
R4724	T16846	T16847	compound	Fig.,4D
R4725	T16728	T16722	prep	on,insertion
R4726	T16847	T16845	pobj	4D,in
R4727	T16848	T16831	punct	.,plotted
R4728	T16729	T16730	det	the,terminus
R4729	T16850	T16851	mark	Although,collected
R4730	T16730	T16728	pobj	terminus,on
R4731	T16851	T16859	advcl	collected,is
R4732	T16852	T16853	compound	survival,data
R4733	T16853	T16851	nsubjpass	data,collected
R4734	T16854	T16853	prep	for,data
R4735	T16731	T16730	compound	carboxy,terminus
R4736	T16855	T16856	compound	control,animals
R4737	T16856	T16854	pobj	animals,for
R4738	T16857	T16851	auxpass	was,collected
R4739	T16732	T16730	prep	of,terminus
R4740	T16858	T16851	neg	not,collected
R4741	T16860	T16859	punct	", ",is
R4742	T16733	T16734	det	an,subunit
R4743	T16861	T16859	nsubj	it,is
R4744	T16862	T16863	advmod	readily,apparent
R4745	T16734	T16732	pobj	subunit,of
R4746	T16863	T16859	acomp	apparent,is
R4747	T16864	T16865	mark	that,compromised
R4748	T16865	T16859	ccomp	compromised,is
R4749	T16735	T16734	amod	analogous,subunit
R4750	T16866	T16865	nsubjpass	survival,compromised
R4751	T16867	T16866	prep	of,survival
R4752	T16868	T16869	det	the,mice
R4753	T16736	T16737	nmod	E.,coli
R4754	T16869	T16867	pobj	mice,of
R4755	T16870	T16869	compound	rescue,mice
R4756	T16871	T16865	auxpass	was,compromised
R4757	T16737	T16734	nmod	coli,subunit
R4758	T16872	T16859	punct	.,is
R4759	T16874	T16875	prep	By,were
R4760	T16738	T16723	prep	with,interfered
R4761	T16876	T16877	nummod	16,weeks
R4762	T16739	T16740	amod	normal,assembly
R4763	T16877	T16874	pobj	weeks,By
R4764	T16878	T16875	punct	", ",were
R4765	T16879	T16880	det	all,mice
R4766	T16740	T16738	pobj	assembly,with
R4767	T16880	T16875	nsubj	mice,were
R4768	T16881	T16880	prep	of,mice
R4769	T16741	T16740	compound	subunit,assembly
R4770	T16882	T16883	compound	Line,A
R4771	T16883	T16881	pobj	A,of
R4772	T16884	T16875	acomp	moribund,were
R4773	T16742	T16743	punct	[,36
R4774	T16885	T16884	cc	and,moribund
R4775	T16886	T16887	advmod	humanely,sacrificed
R4776	T16887	T16884	conj	sacrificed,moribund
R4777	T16743	T16723	parataxis	36,interfered
R4778	T16888	T16875	punct	", ",were
R4779	T16889	T16875	cc	or,were
R4780	T16744	T16743	punct	],36
R4781	T16890	T16891	auxpass	were,found
R4782	T16891	T16875	conj	found,were
R4783	T16892	T16891	advcl	dead,found
R4784	T16745	T16692	punct	.,is
R4785	T16893	T16891	prep	in,found
R4786	T16894	T16895	poss	their,cage
R4787	T16747	T16748	nsubj	It,is
R4788	T16895	T16893	pobj	cage,in
R4789	T16896	T16875	punct	.,were
R4790	T16898	T16899	nsubj	Survival,appeared
R4791	T16749	T16748	advmod	also,is
R4792	T16900	T16898	prep	of,Survival
R4793	T16901	T16902	compound	Line,525A
R4794	T16902	T16900	pobj	525A,of
R4795	T16750	T16748	acomp	possible,is
R4796	T16903	T16904	aux	to,be
R4797	T16904	T16899	xcomp	be,appeared
R4798	T16905	T16906	advmod	somewhat,better
R4799	T16751	T16752	mark	that,was
R4800	T16906	T16904	acomp	better,be
R4801	T16907	T16899	punct	.,appeared
R4802	T16752	T16748	ccomp	was,is
R4803	T16909	T16910	prep	At,were
R4804	T16753	T16754	amod	human,E2
R4805	T16911	T16912	nummod	20,weeks
R4806	T16912	T16909	pobj	weeks,At
R4807	T16913	T16912	prep	of,weeks
R4808	T16754	T16752	nsubj	E2,was
R4809	T16914	T16913	pobj	age,of
R4810	T16915	T16910	punct	", ",were
R4811	T16916	T16917	punct	~,12
R4812	T16755	T16752	neg	not,was
R4813	T16917	T16918	nummod	12,%
R4814	T16918	T16910	nsubj	%,were
R4815	T16919	T16918	prep	of,%
R4816	T16756	T16757	advmod	fully,functional
R4817	T16920	T16919	pobj	mice,of
R4818	T16921	T16922	punct	(,2
R4819	T16922	T16920	parataxis	2,mice
R4820	T16923	T16922	prep	of,2
R4821	T16924	T16923	pobj	16,of
R4822	T16757	T16752	acomp	functional,was
R4823	T16925	T16922	punct	),2
R4824	T16758	T16759	advmod	when,complexed
R4825	T16759	T16752	advcl	complexed,was
R4826	T16760	T16759	prep	with,complexed
R4827	T16926	T16910	advmod	still,were
R4828	T16927	T16910	acomp	alive,were
R4829	T16761	T16762	compound	mouse,E1
R4830	T16928	T16910	punct	.,were
R4831	T16762	T16760	pobj	E1,with
R4832	T16930	T16931	det	These,survivors
R4833	T16931	T16934	nsubj	survivors,died
R4834	T16932	T16931	nummod	two,survivors
R4835	T16763	T16762	cc	and,E1
R4836	T16933	T16931	amod	rare,survivors
R4837	T16764	T16765	compound	E3,subunits
R4838	T16935	T16934	prep	at,died
R4839	T16936	T16937	nummod	40,weeks
R4840	T16937	T16935	pobj	weeks,at
R4841	T16765	T16762	conj	subunits,E1
R4842	T16938	T16936	cc	and,40
R4843	T16766	T16748	punct	.,is
R4844	T16939	T16936	conj	60,40
R4845	T16940	T16937	prep	of,weeks
R4846	T16941	T16940	pobj	age,of
R4847	T16942	T16934	punct	.,died
R4848	T16768	T16769	amod	Human,E2
R4849	T16944	T16945	prep	In,had
R4850	T16946	T16944	pobj	summary,In
R4851	T16769	T16770	nsubj	E2,shares
R4852	T16947	T16945	punct	", ",had
R4853	T16948	T16949	det	these,mice
R4854	T16771	T16772	punct	~,88
R4855	T16949	T16945	nsubj	mice,had
R4856	T16950	T16949	amod	surviving,mice
R4857	T16951	T16952	compound	BCAA,alanine
R4858	T16952	T16954	compound	alanine,ratios
R4859	T16772	T16773	nummod	88,%
R4860	T16953	T16952	punct	/,alanine
R4861	T16954	T16945	dobj	ratios,had
R4862	T16955	T16956	dep	that,were
R4863	T16773	T16774	compound	%,identity
R4864	T16956	T16954	relcl	were,ratios
R4865	T16957	T16956	acomp	intermediate,were
R4866	T16958	T16957	prep	between,intermediate
R4867	T16774	T16770	dobj	identity,shares
R4868	T16959	T16958	pobj	controls,between
R4869	T16960	T16959	cc	and,controls
R4870	T16961	T16959	conj	knockouts,controls
R4871	T16962	T16945	cc	and,had
R4872	T16963	T16964	nsubj	they,expressed
R4873	T16775	T16774	prep	to,identity
R4874	T16964	T16945	conj	expressed,had
R4875	T16965	T16966	punct	~,6
R4876	T16776	T16777	compound	mouse,E2
R4877	T16777	T16775	pobj	E2,to
R4878	T16966	T16969	nummod	6,%
R4879	T16778	T16770	prep	at,shares
R4880	T16967	T16966	quantmod	5,6
R4881	T16968	T16966	punct	–,6
R4882	T16969	T16964	dobj	%,expressed
R4883	T16779	T16780	det	the,level
R4884	T16970	T16969	prep	of,%
R4885	T16971	T16972	amod	normal,activity
R4886	T16780	T16778	pobj	level,at
R4887	T16972	T16970	pobj	activity,of
R4888	T16973	T16972	compound	BCKDH,activity
R4889	T16974	T16972	compound	enzyme,activity
R4890	T16781	T16782	compound	amino,acid
R4891	T16975	T16972	prep	in,activity
R4892	T16976	T16977	det	the,liver
R4893	T16782	T16780	compound	acid,level
R4894	T16977	T16975	pobj	liver,in
R4895	T16978	T16945	punct	.,had
R4896	T16783	T16770	punct	.,shares
R4897	T16980	T16981	det	These,observations
R4898	T16785	T16786	nsubj	We,used
R4899	T16981	T16983	nsubj	observations,are
R4900	T16982	T16981	amod	phenotypic,observations
R4901	T16984	T16985	advmod	remarkably,similar
R4902	T16985	T16983	acomp	similar,are
R4903	T16787	T16786	advmod	also,used
R4904	T16986	T16985	prep	to,similar
R4905	T16987	T16988	det	the,phenotype
R4906	T16988	T16986	pobj	phenotype,to
R4907	T16788	T16789	compound	western,blot
R4908	T16789	T16790	compound	blot,analysis
R4909	T16989	T16988	amod	clinical,phenotype
R4910	T16790	T16786	dobj	analysis,used
R4911	T16990	T16988	acl	observed,phenotype
R4912	T16991	T16990	prep	in,observed
R4913	T16992	T16993	compound	MSUD,patients
R4914	T16791	T16792	aux	to,analyze
R4915	T16993	T16991	pobj	patients,in
R4916	T16994	T16993	prep	with,patients
R4917	T16995	T16996	det	the,form
R4918	T16792	T16786	advcl	analyze,used
R4919	T16996	T16994	pobj	form,with
R4920	T16997	T16996	amod	intermediate,form
R4921	T16998	T16996	prep	of,form
R4922	T16999	T17000	det	the,disease
R4923	T17000	T16998	pobj	disease,of
R4924	T17001	T17002	punct	[,1
R4925	T16793	T16792	dobj	expression,analyze
R4926	T17002	T16983	parataxis	1,are
R4927	T17003	T17002	punct	],1
R4928	T17004	T16983	punct	.,are
R4929	T16794	T16793	prep	of,expression
R4930	T17006	T17007	advmod	Thus,represent
R4931	T16795	T16796	det	the,transgene
R4932	T17008	T17007	punct	", ",represent
R4933	T17009	T17010	det	these,mice
R4934	T17010	T17007	nsubj	mice,represent
R4935	T16796	T16794	pobj	transgene,of
R4936	T17011	T17010	compound	rescue,mice
R4937	T17012	T17013	det	a,model
R4938	T17013	T17007	dobj	model,represent
R4939	T16797	T16796	compound	E2,transgene
R4940	T17014	T17015	advmod	very,useful
R4941	T17015	T17013	amod	useful,model
R4942	T16798	T16792	prep	in,analyze
R4943	T17016	T17013	prep	of,model
R4944	T17017	T17018	det	the,phenotype
R4945	T17018	T17016	pobj	phenotype,of
R4946	T16799	T16798	pobj	brain,in
R4947	T17019	T17018	amod	intermediate,phenotype
R4948	T17020	T17018	compound	MSUD,phenotype
R4949	T17021	T17007	punct	.,represent
R4950	T16800	T16799	punct	", ",brain
R4951	T16801	T16799	conj	kidney,brain
R4952	T16802	T16801	cc	and,kidney
R4953	T16803	T16801	conj	muscle,kidney
R4954	T16804	T16786	punct	.,used
R4955	T16806	T16807	mark	As,shown
R4956	T16807	T16808	advcl	shown,is
R4957	T16809	T16807	prep	in,shown
R4958	T16810	T16811	compound	Figure,3C
R4959	T16811	T16809	pobj	3C,in
R4960	T16812	T16811	punct	", ",3C
R4961	T16813	T16811	conj	D,3C
R4962	T16814	T16813	cc	and,D
R4963	T16815	T16813	conj	3E,D
R4964	T16816	T16807	advmod	respectively,shown
R4965	T16817	T16808	punct	", ",is
R4966	T16818	T16808	nsubj	expression,is
R4967	T16819	T16818	prep	of,expression
R4968	T19826	T19827	det	A,hurdle
R4969	T19827	T19829	nsubj	hurdle,been
R4970	T19828	T19827	amod	major,hurdle
R4971	T19830	T19827	prep	in,hurdle
R4972	T19831	T19830	pcomp	developing,in
R4973	T19832	T19833	amod	new,treatments
R4974	T19833	T19831	dobj	treatments,developing
R4975	T19834	T19833	prep	for,treatments
R4976	T19835	T19834	pobj	MSUD,for
R4977	T19836	T19829	aux	has,been
R4978	T19837	T19838	det	the,lack
R4979	T19838	T19829	attr	lack,been
R4980	T19839	T19838	prep	of,lack
R4981	T19840	T19841	det	a,model
R4982	T19841	T19839	pobj	model,of
R4983	T19842	T19841	amod	practical,model
R4984	T19843	T19841	punct	", ",model
R4985	T19844	T19841	amod	accurate,model
R4986	T19845	T19841	compound	animal,model
R4987	T19846	T19841	prep	of,model
R4988	T19847	T19848	det	the,disease
R4989	T19848	T19846	pobj	disease,of
R4990	T19849	T19829	punct	.,been
R4991	T19851	T19852	det	This,hurdle
R4992	T19852	T19853	nsubjpass	hurdle,overcome
R4993	T19854	T19853	aux	has,overcome
R4994	T19855	T19853	advmod	now,overcome
R4995	T19856	T19853	auxpass	been,overcome
R4996	T19857	T19853	punct	.,overcome
R4997	T19859	T19860	prep	In,describe
R4998	T19861	T19862	det	this,report
R4999	T19862	T19859	pobj	report,In
R5000	T19863	T19860	punct	", ",describe
R5001	T19864	T19860	nsubj	we,describe
R5002	T19865	T19866	det	the,development
R5003	T19866	T19860	dobj	development,describe
R5004	T19867	T19866	cc	and,development
R5005	T19868	T19866	conj	characterization,development
R5006	T19869	T19866	prep	of,development
R5007	T19870	T19871	nummod	two,models
R5008	T19871	T19869	pobj	models,of
R5009	T19872	T19873	advmod	genetically,engineered
R5010	T19873	T19871	amod	engineered,models
R5011	T19874	T19871	compound	mouse,models
R5012	T19875	T19876	dep	that,are
R5013	T19876	T19871	relcl	are,models
R5014	T19877	T19876	advmod	phenotypically,are
R5015	T19878	T19879	advmod	very,similar
R5016	T19879	T19876	acomp	similar,are
R5017	T19880	T19879	prep	to,similar
R5018	T19881	T19882	compound	MSUD,patients
R5019	T19882	T19880	pobj	patients,to
R5020	T19883	T19882	prep	with,patients
R5021	T19884	T19885	det	the,forms
R5022	T19885	T19883	pobj	forms,with
R5023	T19886	T19885	amod	classic,forms
R5024	T19887	T19886	cc	and,classic
R5025	T19888	T19886	conj	intermediate,classic
R5026	T19889	T19885	prep	of,forms
R5027	T19890	T19891	det	the,disease
R5028	T19891	T19889	pobj	disease,of
R5029	T19892	T19860	punct	.,describe
R5030	T19894	T19895	poss	Our,model
R5031	T19895	T19896	nsubjpass	model,created
R5032	T19897	T19895	prep	of,model
R5033	T19898	T19899	amod	classic,MSUD
R5034	T19899	T19897	pobj	MSUD,of
R5035	T19900	T19896	auxpass	was,created
R5036	T19901	T19896	prep	by,created
R5037	T19902	T19903	compound	gene,knockout
R5038	T19903	T19901	pobj	knockout,by
R5039	T19904	T19903	prep	of,knockout
R5040	T19905	T19906	det	the,subunit
R5041	T19906	T19904	pobj	subunit,of
R5042	T19907	T19906	compound	E2,subunit
R5043	T19908	T19906	prep	of,subunit
R5044	T19909	T19908	pobj	BCKDH,of
R5045	T19910	T19896	punct	.,created
R5046	T19912	T19913	det	The,phenotype
R5047	T19913	T19914	nsubj	phenotype,is
R5048	T19915	T19913	prep	of,phenotype
R5049	T19916	T19917	det	these,animals
R5050	T19917	T19915	pobj	animals,of
R5051	T19918	T19917	compound	knockout,animals
R5052	T19919	T19920	advmod	strikingly,similar
R5053	T19920	T19914	acomp	similar,is
R5054	T19921	T19920	prep	to,similar
R5055	T19922	T19921	pobj	humans,to
R5056	T19923	T19922	prep	with,humans
R5057	T19924	T19925	amod	classic,MSUD
R5058	T19925	T19923	pobj	MSUD,with
R5059	T19926	T19914	punct	.,is
R5060	T19928	T19929	compound	Knockout,mice
R5061	T19929	T19930	nsubjpass	mice,born
R5062	T19931	T19930	auxpass	were,born
R5063	T19932	T19930	prep	at,born
R5064	T19933	T19934	det	the,frequency
R5065	T19934	T19932	pobj	frequency,at
R5066	T19935	T19934	amod	expected,frequency
R5067	T19936	T19930	cc	and,born
R5068	T19937	T19930	conj	appeared,born
R5069	T19938	T19937	oprd	normal,appeared
R5070	T19939	T19937	prep	at,appeared
R5071	T19940	T19939	pobj	birth,at
R5072	T19941	T19930	punct	.,born
R5073	T19943	T19944	prep	Within,were
R5074	T19945	T19946	det	a,day
R5075	T19946	T19943	pobj	day,Within
R5076	T19947	T19946	prep	of,day
R5077	T19948	T19947	pobj	birth,of
R5078	T19949	T19943	cc	and,Within
R5079	T19950	T19943	conj	following,Within
R5080	T19951	T19950	pobj	suckling,following
R5081	T19952	T19944	punct	", ",were
R5082	T19953	T19954	compound	blood,levels
R5083	T19954	T19944	nsubj	levels,were
R5084	T19955	T19954	prep	of,levels
R5085	T19956	T19955	pobj	BCAA,of
R5086	T19957	T19958	advmod	markedly,elevated
R5087	T19958	T19944	acomp	elevated,were
R5088	T19959	T19944	punct	.,were
R5089	T19961	T19962	advmod	Concomitantly,decreased
R5090	T19963	T19962	punct	", ",decreased
R5091	T19964	T19962	nsubjpass	levels,decreased
R5092	T19965	T19964	prep	of,levels
R5093	T19966	T19967	det	the,acids
R5094	T19967	T19965	pobj	acids,of
R5095	T19968	T19967	compound	amino,acids
R5096	T19969	T19967	appos	alanine,acids
R5097	T19970	T19969	punct	", ",alanine
R5098	T19971	T19969	conj	glutamate,alanine
R5099	T19972	T19971	punct	", ",glutamate
R5100	T19973	T19971	cc	and,glutamate
R5101	T19974	T19971	conj	glutamine,glutamate
R5102	T19975	T19967	punct	", ",acids
R5103	T19976	T19977	poss	whose,synthesis
R5104	T19977	T19978	dep	synthesis,linked
R5105	T19978	T19967	relcl	linked,acids
R5106	T19979	T19978	auxpass	is,linked
R5107	T19980	T19978	prep	with,linked
R5108	T19981	T19982	amod	normal,metabolism
R5109	T19982	T19980	pobj	metabolism,with
R5110	T19983	T19982	prep	of,metabolism
R5111	T19984	T19983	pobj	BCAA,of
R5112	T19985	T19962	punct	", ",decreased
R5113	T19986	T19962	auxpass	were,decreased
R5114	T19987	T19988	punct	(,Table
R5115	T19988	T19962	parataxis	Table,decreased
R5116	T19989	T19988	nummod	1,Table
R5117	T19990	T19988	punct	),Table
R5118	T19991	T19962	punct	.,decreased
R5119	T19993	T19994	det	The,activity
R5120	T19994	T19995	nsubj	activity,was
R5121	T19996	T19994	prep	of,activity
R5122	T19997	T19996	pobj	BCKDH,of
R5123	T19998	T19994	prep	in,activity
R5124	T19999	T19998	pobj	livers,in
R5125	T20000	T19999	prep	of,livers
R5126	T20001	T20002	amod	homozygous,knockout
R5127	T20002	T20003	compound	knockout,pups
R5128	T20003	T20000	pobj	pups,of
R5129	T20004	T20003	compound	mouse,pups
R5130	T20005	T19995	acomp	undetectable,was
R5131	T20006	T19995	punct	", ",was
R5132	T20007	T19995	advcl	accounting,was
R5133	T20008	T20007	prep	for,accounting
R5134	T20009	T20010	det	the,accumulation
R5135	T20010	T20008	pobj	accumulation,for
R5136	T20011	T20010	prep	of,accumulation
R5137	T20012	T20013	amod	unmetabolized,BCAA
R5138	T20013	T20011	pobj	BCAA,of
R5139	T20014	T19995	punct	.,was
R5140	T20016	T20017	amod	Immunoreactive,protein
R5141	T20017	T20019	nsubj	protein,was
R5142	T20018	T20017	compound	E2,protein
R5143	T20020	T20019	acomp	absent,was
R5144	T20021	T20019	prep	in,was
R5145	T20022	T20021	pobj	liver,in
R5146	T20023	T20022	cc	and,liver
R5147	T20024	T20022	conj	fibroblasts,liver
R5148	T20025	T20022	prep	of,liver
R5149	T20026	T20027	amod	homozygous,pups
R5150	T20027	T20025	pobj	pups,of
R5151	T20028	T20019	punct	.,was
R5152	T20030	T20031	det	The,behavior
R5153	T20031	T20033	nsubj	behavior,resembles
R5154	T20032	T20031	amod	phenotypic,behavior
R5155	T20034	T20031	prep	of,behavior
R5156	T20035	T20036	amod	homozygous,pups
R5157	T20036	T20034	pobj	pups,of
R5158	T20037	T20036	compound	mouse,pups
R5159	T20038	T20033	dobj	symptoms,resembles
R5160	T20039	T20038	acl	seen,symptoms
R5161	T20040	T20039	prep	in,seen
R5162	T20041	T20042	amod	newborn,patients
R5163	T20042	T20040	pobj	patients,in
R5164	T20043	T20042	amod	classic,patients
R5165	T20044	T20042	compound	MSUD,patients
R5166	T20045	T20033	punct	.,resembles
R5167	T20047	T20048	nsubj	These,include
R5168	T20049	T20048	dobj	signs,include
R5169	T20050	T20049	prep	of,signs
R5170	T20051	T20052	amod	neurologic,dysfunction
R5171	T20052	T20050	pobj	dysfunction,of
R5172	T20053	T20054	amod	such,as
R5173	T20054	T20049	prep	as,signs
R5174	T20055	T20054	pobj	seizures,as
R5175	T20056	T20055	punct	", ",seizures
R5176	T20057	T20055	conj	stupor,seizures
R5177	T20058	T20057	punct	", ",stupor
R5178	T20059	T20057	conj	lethargy,stupor
R5179	T20060	T20059	punct	", ",lethargy
R5180	T20061	T20059	conj	loss,lethargy
R5181	T20062	T20061	prep	of,loss
R5182	T20063	T20064	compound	motor,activity
R5183	T20064	T20062	pobj	activity,of
R5184	T20065	T20061	punct	", ",loss
R5185	T20066	T20061	cc	and,loss
R5186	T20067	T20068	amod	respiratory,difficulties
R5187	T20068	T20061	conj	difficulties,loss
R5188	T20069	T20070	punct	[,1
R5189	T20070	T20048	parataxis	1,include
R5190	T20071	T20070	punct	],1
R5191	T20072	T20048	punct	.,include
R5192	T20074	T20075	det	These,symptoms
R5193	T20075	T20077	nsubj	symptoms,result
R5194	T20076	T20075	amod	neurologic,symptoms
R5195	T20078	T20077	aux	may,result
R5196	T20079	T20077	prep	from,result
R5197	T20080	T20081	amod	reduced,levels
R5198	T20081	T20079	pobj	levels,from
R5199	T20082	T20081	prep	of,levels
R5200	T20083	T20082	pobj	glutamate,of
R5201	T20084	T20083	punct	", ",glutamate
R5202	T20085	T20083	conj	glutamine,glutamate
R5203	T20086	T20085	punct	", ",glutamine
R5204	T20087	T20085	conj	alanine,glutamine
R5205	T20088	T20087	punct	", ",alanine
R5206	T20089	T20087	cc	and,alanine
R5207	T20090	T20091	amod	other,acids
R5208	T20091	T20087	conj	acids,alanine
R5209	T20092	T20091	amod	similar,acids
R5210	T20093	T20091	amod	neuroactive,acids
R5211	T20094	T20091	compound	amino,acids
R5212	T20095	T20083	punct	", ",glutamate
R5213	T20096	T20097	dep	which,considered
R5214	T20097	T20083	relcl	considered,glutamate
R5215	T20098	T20097	auxpass	are,considered
R5216	T20099	T20100	det	the,culprit
R5217	T20100	T20097	oprd	culprit,considered
R5218	T20101	T20100	prep	for,culprit
R5219	T20102	T20103	compound	MSUD,encephalopathies
R5220	T20103	T20101	pobj	encephalopathies,for
R5221	T20104	T20100	prep	in,culprit
R5222	T20105	T20104	pobj	patients,in
R5223	T20106	T20107	punct	[,37
R5224	T20107	T20077	parataxis	37,result
R5225	T20108	T20107	nummod	1,37
R5226	T20109	T20107	punct	",",37
R5227	T20110	T20107	punct	],37
R5228	T20111	T20077	punct	.,result
R5229	T20113	T20114	advmod	Finally,died
R5230	T20115	T20114	punct	", ",died
R5231	T20116	T20117	advmod	nearly,all
R5232	T20117	T20114	nsubj	all,died
R5233	T20118	T20117	prep	of,all
R5234	T20119	T20120	det	the,pups
R5235	T20120	T20118	pobj	pups,of
R5236	T20121	T20120	amod	homozygous,pups
R5237	T20122	T20114	prep	within,died
R5238	T20123	T20124	nummod	72,hours
R5239	T20124	T20122	pobj	hours,within
R5240	T20125	T20124	prep	of,hours
R5241	T20126	T20125	pobj	birth,of
R5242	T20127	T20114	punct	.,died
R5243	T20129	T20130	det	This,lethality
R5244	T20130	T20132	nsubj	lethality,is
R5245	T20131	T20130	amod	neonatal,lethality
R5246	T20133	T20134	advmod	likely,due
R5247	T20134	T20132	prep	due,is
R5248	T20135	T20134	pcomp	to,due
R5249	T20136	T20137	det	the,accumulation
R5250	T20137	T20134	pobj	accumulation,due
R5251	T20138	T20137	prep	of,accumulation
R5252	T20139	T20138	pobj	BCAA,of
R5253	T20140	T20137	prep	to,accumulation
R5254	T20141	T20142	amod	neurotoxic,levels
R5255	T20142	T20140	pobj	levels,to
R5256	T20143	T20142	punct	", ",levels
R5257	T20144	T20142	conj	ketoacidosis,levels
R5258	T20145	T20144	punct	", ",ketoacidosis
R5259	T20146	T20147	compound	brain,edema
R5260	T20147	T20144	conj	edema,ketoacidosis
R5261	T20148	T20147	punct	", ",edema
R5262	T20149	T20147	conj	dehydration,edema
R5263	T20150	T20149	punct	", ",dehydration
R5264	T20151	T20149	cc	and,dehydration
R5265	T20152	T20149	conj	malnutrition,dehydration
R5266	T20153	T20154	mark	as,observed
R5267	T20154	T20132	advcl	observed,is
R5268	T20155	T20154	prep	in,observed
R5269	T20156	T20157	det	the,calf
R5270	T20157	T20155	pobj	calf,in
R5271	T20158	T20157	compound	MSUD,calf
R5272	T20159	T20160	punct	[,17
R5273	T20160	T20157	parataxis	17,calf
R5274	T20161	T20160	punct	],17
R5275	T20162	T20155	cc	and,in
R5276	T20163	T20155	conj	in,in
R5277	T20164	T20165	amod	classic,patients
R5278	T20165	T20163	pobj	patients,in
R5279	T20166	T20165	compound	MSUD,patients
R5280	T20167	T20168	punct	[,1
R5281	T20168	T20165	parataxis	1,patients
R5282	T20169	T20168	punct	],1
R5283	T20170	T20132	punct	.,is
R5284	T20172	T20173	amod	Heterozygous,knockouts
R5285	T20173	T20174	nsubj	knockouts,were
R5286	T20175	T20174	acomp	normal,were
R5287	T20176	T20174	cc	and,were
R5288	T20177	T20174	conj	had,were
R5289	T20178	T20179	amod	normal,levels
R5290	T20179	T20177	dobj	levels,had
R5291	T20180	T20179	prep	of,levels
R5292	T20181	T20180	pobj	BCAA,of
R5293	T20182	T20177	prep	despite,had
R5294	T20183	T20182	pcomp	having,despite
R5295	T20184	T20185	advmod	approximately,half
R5296	T20185	T20183	dobj	half,having
R5297	T20186	T20185	prep	of,half
R5298	T20187	T20188	nmod	BCKDH,activity
R5299	T20188	T20186	pobj	activity,of
R5300	T20189	T20188	amod	enzymatic,activity
R5301	T20190	T20174	punct	.,were
R5302	T20192	T20193	prep	From,represents
R5303	T20194	T20195	det	the,studies
R5304	T20195	T20192	pobj	studies,From
R5305	T20196	T20195	compound	characterization,studies
R5306	T20197	T20195	acl	completed,studies
R5307	T20198	T20199	advmod	thus,far
R5308	T20199	T20197	advmod	far,completed
R5309	T20200	T20193	punct	", ",represents
R5310	T20201	T20202	det	the,mouse
R5311	T20202	T20193	nsubj	mouse,represents
R5312	T20203	T20204	amod	null,mutation
R5313	T20204	T20202	compound	mutation,mouse
R5314	T20205	T20193	advmod	accurately,represents
R5315	T20206	T20207	det	a,model
R5316	T20207	T20193	dobj	model,represents
R5317	T20208	T20207	prep	of,model
R5318	T20209	T20210	amod	classic,MSUD
R5319	T20210	T20208	pobj	MSUD,of
R5320	T20211	T20193	cc	and,represents
R5321	T20212	T20193	conj	appears,represents
R5322	T20213	T20214	aux	to,be
R5323	T20214	T20212	xcomp	be,appears
R5324	T20215	T20216	det	a,model
R5325	T20216	T20214	attr	model,be
R5326	T20217	T20216	amod	faithful,model
R5327	T20218	T20216	prep	of,model
R5328	T20219	T20220	det	the,disease
R5329	T20220	T20218	pobj	disease,of
R5330	T20221	T20220	amod	human,disease
R5331	T20222	T20214	prep	with,be
R5332	T20223	T20222	pobj	respect,with
R5333	T20224	T20223	prep	to,respect
R5334	T20225	T20226	amod	several,phenotypes
R5335	T20226	T20224	pobj	phenotypes,to
R5336	T20227	T20226	amod	biochemical,phenotypes
R5337	T20228	T20229	punct	[,1
R5338	T20229	T20212	parataxis	1,appears
R5339	T20230	T20229	punct	],1
R5340	T20231	T20193	punct	.,represents
R5341	T20233	T20234	aux	To,create
R5342	T20234	T20235	advcl	create,used
R5343	T20236	T20237	det	a,model
R5344	T20237	T20234	dobj	model,create
R5345	T20238	T20237	prep	of,model
R5346	T20239	T20240	amod	intermediate,MSUD
R5347	T20240	T20238	pobj	MSUD,of
R5348	T20241	T20235	punct	", ",used
R5349	T20242	T20235	nsubj	we,used
R5350	T20243	T20244	det	a,strategy
R5351	T20244	T20235	dobj	strategy,used
R5352	T20245	T20244	amod	transgenic,strategy
R5353	T20246	T20247	aux	to,express
R5354	T20247	T20235	advcl	express,used
R5355	T20248	T20249	amod	human,E2
R5356	T20249	T20247	dobj	E2,express
R5357	T20250	T20247	prep	in,express
R5358	T20251	T20252	det	the,liver
R5359	T20252	T20250	pobj	liver,in
R5360	T20253	T20252	prep	of,liver
R5361	T20254	T20255	compound	E2,mice
R5362	T20255	T20253	pobj	mice,of
R5363	T20256	T20255	compound	knockout,mice
R5364	T20257	T20235	punct	.,used
R5365	T20259	T20260	mark	As,mentioned
R5366	T20260	T20261	advcl	mentioned,die
R5367	T20262	T20260	advmod	above,mentioned
R5368	T20263	T20261	punct	", ",die
R5369	T20264	T20265	compound	E2,knockouts
R5370	T20265	T20261	nsubj	knockouts,die
R5371	T20266	T20265	prep	without,knockouts
R5372	T20267	T20268	npadvmod	transgene,derived
R5373	T20268	T20269	amod	derived,E2
R5374	T20269	T20266	pobj	E2,without
R5375	T20270	T20261	prep	during,die
R5376	T20271	T20272	det	the,period
R5377	T20272	T20270	pobj	period,during
R5378	T20273	T20274	amod	early,neonatal
R5379	T20274	T20272	amod	neonatal,period
R5380	T20275	T20261	punct	.,die
R5381	T20277	T20278	nsubj	We,show
R5382	T20279	T20280	mark	that,is
R5383	T20280	T20278	ccomp	is,show
R5384	T20281	T20280	nsubj	expression,is
R5385	T20282	T20281	prep	of,expression
R5386	T20283	T20284	det	a,transgene
R5387	T20284	T20282	pobj	transgene,of
R5388	T20285	T20284	amod	human,transgene
R5389	T20286	T20284	compound	E2,transgene
R5390	T20287	T20281	prep	in,expression
R5391	T20288	T20289	det	the,liver
R5392	T20289	T20287	pobj	liver,in
R5393	T20290	T20289	prep	of,liver
R5394	T20291	T20292	det	these,mice
R5395	T20292	T20290	pobj	mice,of
R5396	T20293	T20292	compound	knockout,mice
R5397	T20294	T20280	acomp	able,is
R5398	T20295	T20296	aux	to,rescue
R5399	T20296	T20294	xcomp	rescue,able
R5400	T20297	T20298	det	the,lethality
R5401	T20298	T20296	dobj	lethality,rescue
R5402	T20299	T20298	amod	neonatal,lethality
R5403	T20300	T20278	punct	.,show
R5404	T20302	T20303	nsubj	Many,survived
R5405	T20304	T20302	prep	of,Many
R5406	T20305	T20306	det	the,mice
R5407	T20306	T20304	pobj	mice,of
R5408	T20307	T20306	compound	rescue,mice
R5409	T20308	T20303	prep	to,survived
R5410	T20309	T20308	pobj	adulthood,to
R5411	T20310	T20303	punct	.,survived
R5412	T20312	T20313	nsubj	It,is
R5413	T20314	T20313	acomp	interesting,is
R5414	T20315	T20316	aux	to,note
R5415	T20316	T20313	xcomp	note,is
R5416	T20317	T20318	mark	that,was
R5417	T20318	T20316	ccomp	was,note
R5418	T20319	T20318	prep	in,was
R5419	T20320	T20321	det	these,lines
R5420	T20321	T20319	pobj	lines,in
R5421	T20322	T20321	compound	mouse,lines
R5422	T20323	T20324	advmod	only,6
R5423	T20324	T20328	nummod	6,%
R5424	T20325	T20324	punct	~,6
R5425	T20326	T20324	quantmod	5,6
R5426	T20327	T20324	punct	–,6
R5427	T20328	T20318	nsubj	%,was
R5428	T20329	T20328	prep	of,%
R5429	T20330	T20331	amod	normal,activity
R5430	T20331	T20329	pobj	activity,of
R5431	T20332	T20331	compound	BCKDH,activity
R5432	T20333	T20331	prep	in,activity
R5433	T20334	T20335	det	the,liver
R5434	T20335	T20333	pobj	liver,in
R5435	T20336	T20318	acomp	sufficient,was
R5436	T20337	T20338	aux	to,allow
R5437	T20338	T20336	xcomp	allow,sufficient
R5438	T20339	T20338	dobj	survival,allow
R5439	T20340	T20313	punct	.,is
R5440	T20342	T20343	nsubj	We,demonstrated
R5441	T20344	T20343	advmod	also,demonstrated
R5442	T20345	T20346	mark	that,were
R5443	T20346	T20343	ccomp	were,demonstrated
R5444	T20347	T20348	compound	BCAA,levels
R5445	T20348	T20346	nsubj	levels,were
R5446	T20349	T20348	prep	in,levels
R5447	T20350	T20349	pobj	blood,in
R5448	T20351	T20350	prep	of,blood
R5449	T20352	T20353	det	these,mice
R5450	T20353	T20351	pobj	mice,of
R5451	T20354	T20353	compound	rescue,mice
R5452	T20355	T20346	acomp	intermediate,were
R5453	T20356	T20346	prep	between,were
R5454	T20357	T20356	pobj	controls,between
R5455	T20358	T20357	cc	and,controls
R5456	T20359	T20357	conj	knockouts,controls
R5457	T20360	T20343	punct	.,demonstrated
R5458	T20362	T20363	det	The,hallmarks
R5459	T20363	T20364	nsubj	hallmarks,are
R5460	T20365	T20363	prep	of,hallmarks
R5461	T20366	T20367	amod	intermediate,patients
R5462	T20367	T20365	pobj	patients,of
R5463	T20368	T20367	nmod	MSUD,patients
R5464	T20369	T20367	amod	human,patients
R5465	T20370	T20371	advmod	persistently,increased
R5466	T20371	T20372	amod	increased,levels
R5467	T20372	T20364	attr	levels,are
R5468	T20373	T20372	prep	of,levels
R5469	T20374	T20375	nmod	BCAA,activity
R5470	T20375	T20373	pobj	activity,of
R5471	T20376	T20374	cc	and,BCAA
R5472	T20377	T20374	conj	BCKDH,BCAA
R5473	T20378	T20372	prep	in,levels
R5474	T20379	T20380	det	the,range
R5475	T20380	T20378	pobj	range,in
R5476	T20381	T20380	prep	of,range
R5477	T20382	T20383	quantmod	3,30
R5478	T20383	T20385	nummod	30,%
R5479	T20384	T20383	punct	–,30
R5480	T20385	T20381	pobj	%,of
R5481	T20386	T20385	prep	of,%
R5482	T20387	T20386	pobj	normal,of
R5483	T20388	T20389	punct	[,1
R5484	T20389	T20364	parataxis	1,are
R5485	T20390	T20389	punct	],1
R5486	T20391	T20364	punct	.,are
R5487	T20393	T20394	prep	Because,represent
R5488	T20395	T20393	pcomp	of,Because
R5489	T20396	T20397	det	the,similarities
R5490	T20397	T20393	pobj	similarities,Because
R5491	T20398	T20397	amod	phenotypic,similarities
R5492	T20399	T20397	prep	of,similarities
R5493	T20400	T20401	det	the,mice
R5494	T20401	T20399	pobj	mice,of
R5495	T20402	T20401	compound	rescue,mice
R5496	T20403	T20397	prep	to,similarities
R5497	T20404	T20405	det	the,patients
R5498	T20405	T20403	pobj	patients,to
R5499	T20406	T20405	amod	human,patients
R5500	T20407	T20394	punct	", ",represent
R5501	T20408	T20409	det	these,mice
R5502	T20409	T20394	nsubj	mice,represent
R5503	T20410	T20411	advmod	genetically,engineered
R5504	T20411	T20409	amod	engineered,mice
R5505	T20412	T20413	det	a,model
R5506	T20413	T20394	dobj	model,represent
R5507	T20414	T20413	amod	useful,model
R5508	T20415	T20416	amod	small,animal
R5509	T20416	T20413	compound	animal,model
R5510	T20417	T20413	prep	of,model
R5511	T20418	T20419	det	the,form
R5512	T20419	T20417	pobj	form,of
R5513	T20420	T20419	amod	intermediate,form
R5514	T20421	T20419	prep	of,form
R5515	T20422	T20421	pobj	MSUD,of
R5516	T20423	T20394	punct	.,represent
R5517	T20425	T20426	det	The,approach
R5518	T20426	T20428	nsubjpass	approach,based
R5519	T20427	T20426	amod	transgenic,approach
R5520	T20429	T20430	dep	that,used
R5521	T20430	T20426	relcl	used,approach
R5522	T20431	T20430	auxpass	was,used
R5523	T20432	T20433	aux	to,create
R5524	T20433	T20430	advcl	create,used
R5525	T20434	T20435	det	the,model
R5526	T20435	T20433	dobj	model,create
R5527	T20436	T20435	amod	intermediate,model
R5528	T20437	T20435	compound	MSUD,model
R5529	T20438	T20428	auxpass	was,based
R5530	T20439	T20428	prep	on,based
R5531	T20440	T20441	det	the,system
R5532	T20441	T20439	pobj	system,on
R5533	T20442	T20443	npadvmod	tetracycline,regulated
R5534	T20443	T20441	amod	regulated,system
R5535	T20444	T20445	compound	gene,switch
R5536	T20445	T20441	compound	switch,system
R5537	T20446	T20447	dep	that,used
R5538	T20447	T20441	relcl	used,system
R5539	T20448	T20447	aux	has,used
R5540	T20449	T20447	auxpass	been,used
R5541	T20450	T20447	prep	with,used
R5542	T20451	T20452	amod	great,success
R5543	T20452	T20450	pobj	success,with
R5544	T20453	T20447	prep	in,used
R5545	T20454	T20455	amod	other,studies
R5546	T20455	T20453	pobj	studies,in
R5547	T20456	T20447	punct	", ",used
R5548	T20457	T20447	prep	for,used
R5549	T20458	T20457	pobj	example,for
R5550	T20459	T20460	punct	[,34
R5551	T20460	T20428	parataxis	34,based
R5552	T20461	T20460	punct	],34
R5553	T20462	T20428	punct	.,based
R5554	T20464	T20465	det	The,strategy
R5555	T20465	T20466	nsubj	strategy,was
R5556	T20467	T20465	prep	behind,strategy
R5557	T20468	T20469	poss	our,approach
R5558	T20469	T20467	pobj	approach,behind
R5559	T20470	T20471	aux	to,create
R5560	T20471	T20466	xcomp	create,was
R5561	T20472	T20471	dobj	mice,create
R5562	T20473	T20472	prep	with,mice
R5563	T20474	T20475	det	an,phenotype
R5564	T20475	T20473	pobj	phenotype,with
R5565	T20476	T20475	amod	intermediate,phenotype
R5566	T20477	T20475	compound	MSUD,phenotype
R5567	T20478	T20479	dep	that,converted
R5568	T20479	T20475	relcl	converted,phenotype
R5569	T20480	T20479	aux	could,converted
R5570	T20481	T20479	auxpass	be,converted
R5571	T20482	T20479	prep	to,converted
R5572	T20483	T20484	det	the,phenotype
R5573	T20484	T20482	pobj	phenotype,to
R5574	T20485	T20484	amod	classic,phenotype
R5575	T20486	T20479	prep	at,converted
R5576	T20487	T20488	det	the,investigator
R5577	T20488	T20489	poss	investigator,discretion
R5578	T20489	T20486	pobj	discretion,at
R5579	T20490	T20488	case	's,investigator
R5580	T20491	T20479	prep	by,converted
R5581	T20492	T20491	pcomp	turning,by
R5582	T20493	T20492	prt	off,turning
R5583	T20494	T20495	det	the,transgene
R5584	T20495	T20492	dobj	transgene,turning
R5585	T20496	T20495	amod	rescuing,transgene
R5586	T20497	T20466	punct	.,was
R5587	T20499	T20500	advmod	However,were
R5588	T20501	T20500	punct	", ",were
R5589	T20502	T20500	nsubj	we,were
R5590	T20503	T20500	acomp	unable,were
R5591	T20504	T20505	aux	to,turn
R5592	T20505	T20503	xcomp	turn,unable
R5593	T20506	T20505	advmod	consistently,turn
R5594	T20507	T20505	prt	off,turn
R5595	T20508	T20509	det	the,cassette
R5596	T20509	T20505	dobj	cassette,turn
R5597	T20510	T20509	amod	human,cassette
R5598	T20511	T20509	compound	E2,cassette
R5599	T20512	T20509	compound	expression,cassette
R5600	T20513	T20505	prep	by,turn
R5601	T20514	T20515	det	the,analogue
R5602	T20515	T20513	pobj	analogue,by
R5603	T20516	T20515	amod	potent,analogue
R5604	T20517	T20515	compound	tetracycline,analogue
R5605	T20518	T20515	punct	", ",analogue
R5606	T20519	T20515	appos	doxycycline,analogue
R5607	T20520	T20505	prep	in,turn
R5608	T20521	T20520	pobj	either,in
R5609	T20522	T20521	prep	of,either
R5610	T20523	T20524	det	the,lines
R5611	T20524	T20522	pobj	lines,of
R5612	T20525	T20524	nummod	two,lines
R5613	T20526	T20524	amod	transgenic,lines
R5614	T20527	T20524	acl	tested,lines
R5615	T20528	T20529	punct	(,shown
R5616	T20529	T20500	parataxis	shown,were
R5617	T20530	T20529	nsubj	data,shown
R5618	T20531	T20529	neg	not,shown
R5619	T20532	T20529	punct	),shown
R5620	T20533	T20500	punct	.,were
R5621	T20535	T20536	det	The,reason
R5622	T20536	T20537	nsubj	reason,is
R5623	T20538	T20539	det	these,lines
R5624	T20539	T20541	nsubj	lines,were
R5625	T20540	T20539	nummod	two,lines
R5626	T20541	T20536	advcl	were,reason
R5627	T20542	T20541	acomp	unresponsive,were
R5628	T20543	T20542	prep	to,unresponsive
R5629	T20544	T20543	pobj	doxycycline,to
R5630	T20545	T20537	acomp	unknown,is
R5631	T20546	T20537	punct	.,is
R5632	T20548	T20549	nsubj	It,is
R5633	T20550	T20549	acomp	conceivable,is
R5634	T20551	T20552	mark	that,was
R5635	T20552	T20549	ccomp	was,is
R5636	T20553	T20554	det	the,site
R5637	T20554	T20552	nsubj	site,was
R5638	T20555	T20554	compound	integration,site
R5639	T20556	T20554	prep	of,site
R5640	T20557	T20558	det	the,transgenes
R5641	T20558	T20556	pobj	transgenes,of
R5642	T20559	T20552	neg	not,was
R5643	T20560	T20552	acomp	permissive,was
R5644	T20561	T20560	prep	for,permissive
R5645	T20562	T20563	amod	regulated,expression
R5646	T20563	T20561	pobj	expression,for
R5647	T20564	T20549	punct	.,is
R5648	T20566	T20567	nsubjpass	Screening,needed
R5649	T20568	T20566	prep	of,Screening
R5650	T20569	T20570	amod	additional,lines
R5651	T20570	T20568	pobj	lines,of
R5652	T20571	T20567	aux	may,needed
R5653	T20572	T20567	auxpass	be,needed
R5654	T20573	T20574	aux	to,find
R5655	T20574	T20567	advcl	find,needed
R5656	T20575	T20574	dobj	lines,find
R5657	T20576	T20577	dep	that,allow
R5658	T20577	T20575	relcl	allow,lines
R5659	T20578	T20577	prep	for,allow
R5660	T20579	T20578	pobj	survival,for
R5661	T20580	T20577	cc	and,allow
R5662	T20581	T20582	aux	can,regulated
R5663	T20582	T20577	conj	regulated,allow
R5664	T20583	T20582	advmod	also,regulated
R5665	T20584	T20582	auxpass	be,regulated
R5666	T20585	T20567	punct	.,needed
R5667	T20587	T20588	det	The,models
R5668	T20588	T20589	nsubj	models,are
R5669	T20590	T20588	acl	described,models
R5670	T20591	T20590	prep	in,described
R5671	T20592	T20593	det	this,communication
R5672	T20593	T20591	pobj	communication,in
R5673	T20594	T20595	amod	important,advances
R5674	T20595	T20589	attr	advances,are
R5675	T20596	T20595	prep	over,advances
R5676	T20597	T20598	det	the,models
R5677	T20598	T20596	pobj	models,over
R5678	T20599	T20600	advmod	previously,described
R5679	T20600	T20598	amod	described,models
R5680	T20601	T20589	punct	.,are
R5681	T20603	T20604	det	An,mouse
R5682	T20604	T20606	nsubjpass	mouse,created
R5683	T20605	T20604	compound	ENU,mouse
R5684	T20607	T20604	acl	resembling,mouse
R5685	T20608	T20609	amod	human,MSUD
R5686	T20609	T20607	dobj	MSUD,resembling
R5687	T20610	T20606	auxpass	was,created
R5688	T20611	T20606	advmod	previously,created
R5689	T20612	T20606	prep	by,created
R5690	T20613	T20612	pcomp	disrupting,by
R5691	T20614	T20615	det	the,gene
R5692	T20615	T20613	dobj	gene,disrupting
R5693	T20616	T20615	amod	mitochondrial,gene
R5694	T20617	T20615	compound	BCAT,gene
R5695	T20618	T20619	punct	[,20
R5696	T20619	T20606	parataxis	20,created
R5697	T20620	T20619	punct	],20
R5698	T20621	T20606	punct	.,created
R5699	T20623	T20624	det	The,activity
R5700	T20624	T20626	nsubj	activity,was
R5701	T20625	T20624	compound	BCKDH,activity
R5702	T20627	T20624	prep	in,activity
R5703	T20628	T20629	det	the,liver
R5704	T20629	T20627	pobj	liver,in
R5705	T20630	T20629	cc	and,liver
R5706	T20631	T20629	conj	muscle,liver
R5707	T20632	T20629	prep	of,liver
R5708	T20633	T20634	det	this,mouse
R5709	T20634	T20632	pobj	mouse,of
R5710	T20635	T20626	acomp	normal,was
R5711	T20636	T20637	advmod	even,were
R5712	T20637	T20626	advcl	were,was
R5713	T20638	T20637	mark	though,were
R5714	T20639	T20640	det	the,levels
R5715	T20640	T20637	nsubj	levels,were
R5716	T20641	T20640	compound	blood,levels
R5717	T20642	T20640	compound	BCAA,levels
R5718	T20643	T20644	advmod	markedly,elevated
R5719	T20644	T20637	acomp	elevated,were
R5720	T20645	T20626	punct	.,was
R5721	T20647	T20648	mark	While,is
R5722	T20648	T20650	advcl	is,is
R5723	T20649	T20648	nsubj	this,is
R5724	T20651	T20652	det	an,model
R5725	T20652	T20648	attr	model,is
R5726	T20653	T20652	amod	interesting,model
R5727	T20654	T20650	punct	", ",is
R5728	T20655	T20650	nsubj	it,is
R5729	T20656	T20650	neg	not,is
R5730	T20657	T20658	det	a,model
R5731	T20658	T20650	attr	model,is
R5732	T20659	T20658	amod	true,model
R5733	T20660	T20658	prep	of,model
R5734	T20661	T20660	pobj	MSUD,of
R5735	T20662	T20663	mark	because,is
R5736	T20663	T20650	advcl	is,is
R5737	T20664	T20665	det	the,mutation
R5738	T20665	T20663	nsubj	mutation,is
R5739	T20666	T20663	neg	not,is
R5740	T20667	T20663	prep	in,is
R5741	T20668	T20667	pobj	BCKDH,in
R5742	T20669	T20663	cc	and,is
R5743	T20670	T20671	det	the,levels
R5744	T20671	T20672	nsubj	levels,are
R5745	T20672	T20663	conj	are,is
R5746	T20673	T20671	prep	of,levels
R5747	T20674	T20673	pobj	BCKDH,of
R5748	T20675	T20672	acomp	normal,are
R5749	T20676	T20650	punct	.,is
R5750	T20678	T20679	advmod	Furthermore,described
R5751	T20680	T20679	punct	", ",described
R5752	T20681	T20682	det	no,case
R5753	T20682	T20679	nsubjpass	case,described
R5754	T20683	T20682	prep	of,case
R5755	T20790	T20789	compound	MSUD,models
R5756	T20791	T20789	compound	mouse,models
R5757	T20792	T20793	aux	to,test
R5758	T20793	T20785	xcomp	test,is
R5759	T20794	T20795	amod	novel,treatments
R5760	T20795	T20793	dobj	treatments,test
R5761	T20796	T20797	amod	such,as
R5762	T20797	T20795	prep	as,treatments
R5763	T20798	T20799	npadvmod	gene,based
R5764	T20799	T20807	amod	based,therapies
R5765	T20800	T20801	punct	[,38
R5766	T20801	T20798	parataxis	38,gene
R5767	T20802	T20803	punct	-,41
R5768	T20803	T20801	prep	41,38
R5769	T20804	T20801	punct	],38
R5770	T20805	T20798	cc	and,gene
R5771	T20806	T20798	conj	cell,gene
R5772	T20684	T20683	pobj	MSUD,of
R5773	T20807	T20797	pobj	therapies,as
R5774	T20685	T20679	aux	has,described
R5775	T20686	T20679	auxpass	been,described
R5776	T20808	T20809	punct	(,hepatocytes
R5777	T20687	T20679	advcl	attributing,described
R5778	T20688	T20689	det	this,disease
R5779	T20809	T20807	parataxis	hepatocytes,therapies
R5780	T20689	T20687	dobj	disease,attributing
R5781	T20690	T20687	prep	to,attributing
R5782	T20691	T20692	compound	BCAT,deficiency
R5783	T20810	T20809	advmod	e.g.,hepatocytes
R5784	T20692	T20690	pobj	deficiency,to
R5785	T20693	T20679	punct	.,described
R5786	T20811	T20809	punct	", ",hepatocytes
R5787	T20695	T20696	prep	In,described
R5788	T20812	T20813	punct	[,43
R5789	T20697	T20695	pobj	addition,In
R5790	T20698	T20697	prep	to,addition
R5791	T20813	T20809	parataxis	43,hepatocytes
R5792	T20699	T20700	det	this,model
R5793	T20700	T20698	pobj	model,to
R5794	T20701	T20700	compound	mouse,model
R5795	T20702	T20696	punct	", ",described
R5796	T20814	T20813	nummod	42,43
R5797	T20703	T20704	det	a,model
R5798	T20704	T20696	nsubjpass	model,described
R5799	T20705	T20704	compound	cow,model
R5800	T20706	T20704	prep	of,model
R5801	T20707	T20706	pobj	MSUD,of
R5802	T20708	T20696	aux	has,described
R5803	T20815	T20813	punct	",",43
R5804	T20709	T20696	advmod	also,described
R5805	T20710	T20696	auxpass	been,described
R5806	T20711	T20696	advmod	previously,described
R5807	T20816	T20813	punct	],43
R5808	T20712	T20713	punct	[,17
R5809	T20713	T20696	parataxis	17,described
R5810	T20714	T20715	punct	-,19
R5811	T20817	T20809	cc	or,hepatocytes
R5812	T20715	T20713	prep	19,17
R5813	T20716	T20713	punct	],17
R5814	T20717	T20696	punct	.,described
R5815	T20818	T20819	amod	embryonic,cells
R5816	T20719	T20720	advmod	However,is
R5817	T20819	T20809	conj	cells,hepatocytes
R5818	T20721	T20720	punct	", ",is
R5819	T20722	T20720	prep	due,is
R5820	T20723	T20722	pcomp	to,due
R5821	T20724	T20725	amod	practical,constraints
R5822	T20820	T20819	compound	stem,cells
R5823	T20725	T20722	pobj	constraints,due
R5824	T20726	T20725	acl	imposed,constraints
R5825	T20821	T20822	punct	[,44
R5826	T20727	T20726	agent	by,imposed
R5827	T20728	T20729	amod	such,model
R5828	T20729	T20727	pobj	model,by
R5829	T20822	T20819	parataxis	44,cells
R5830	T20730	T20729	det	a,model
R5831	T20731	T20729	amod	large,model
R5832	T20732	T20729	compound	animal,model
R5833	T20823	T20822	punct	],44
R5834	T20733	T20722	cc	and,due
R5835	T20734	T20722	conj	due,due
R5836	T20735	T20734	pcomp	to,due
R5837	T20824	T20809	punct	),hepatocytes
R5838	T20736	T20737	det	the,observation
R5839	T20737	T20734	pobj	observation,due
R5840	T20738	T20737	prep	of,observation
R5841	T20825	T20785	punct	.,is
R5842	T20739	T20738	pobj	differences,of
R5843	T20740	T20739	prep	between,differences
R5844	T20827	T20828	advcl	Relevant,highlight
R5845	T20741	T20742	det	the,model
R5846	T20742	T20740	pobj	model,between
R5847	T20829	T20827	prep	to,Relevant
R5848	T20743	T20742	compound	MSUD,model
R5849	T20744	T20742	compound	cow,model
R5850	T20745	T20742	cc	and,model
R5851	T20746	T20747	compound	MSUD,humans
R5852	T20747	T20742	conj	humans,model
R5853	T20748	T20749	punct	[,1
R5854	T20749	T20734	parataxis	1,due
R5855	T20830	T20831	compound	gene,therapy
R5856	T20750	T20749	punct	],1
R5857	T20751	T20720	punct	", ",is
R5858	T20752	T20753	det	this,model
R5859	T20831	T20829	pobj	therapy,to
R5860	T20753	T20720	nsubj	model,is
R5861	T20754	T20720	advmod	also,is
R5862	T20755	T20720	prep	of,is
R5863	T20832	T20828	punct	", ",highlight
R5864	T20756	T20757	amod	limited,utility
R5865	T20833	T20834	amod	recent,problems
R5866	T20757	T20755	pobj	utility,of
R5867	T20758	T20720	punct	.,is
R5868	T20760	T20761	prep	In,are
R5869	T20834	T20828	nsubj	problems,highlight
R5870	T20762	T20760	pobj	contrast,In
R5871	T20763	T20761	punct	", ",are
R5872	T20835	T20834	prep	with,problems
R5873	T20764	T20765	det	the,models
R5874	T20765	T20761	nsubj	models,are
R5875	T20766	T20765	amod	murine,models
R5876	T20836	T20837	compound	gene,therapy
R5877	T20767	T20765	acl	described,models
R5878	T20768	T20767	prep	in,described
R5879	T20769	T20770	det	this,report
R5880	T20837	T20835	pobj	therapy,with
R5881	T20770	T20768	pobj	report,in
R5882	T20771	T20772	advmod	more,valid
R5883	T20772	T20761	acomp	valid,are
R5884	T20838	T20834	prep	in,problems
R5885	T20773	T20772	cc	and,valid
R5886	T20774	T20772	conj	appropriate,valid
R5887	T20775	T20774	prep	for,appropriate
R5888	T20839	T20838	pobj	humans,in
R5889	T20776	T20777	amod	modeling,MSUD
R5890	T20777	T20775	pobj	MSUD,for
R5891	T20778	T20777	amod	human,MSUD
R5892	T20840	T20841	det	the,importance
R5893	T20779	T20761	punct	.,are
R5894	T20841	T20828	dobj	importance,highlight
R5895	T20781	T20782	det	The,opportunity
R5896	T20782	T20785	nsubj	opportunity,is
R5897	T20783	T20784	advmod	most,significant
R5898	T20784	T20782	amod	significant,opportunity
R5899	T20842	T20841	cc	and,importance
R5900	T20786	T20782	acl	presented,opportunity
R5901	T20787	T20786	agent	by,presented
R5902	T20788	T20789	det	the,models
R5903	T20789	T20787	pobj	models,by
R5904	T20843	T20844	amod	critical,need
R5905	T20844	T20841	conj	need,importance
R5906	T20845	T20841	prep	of,importance
R5907	T20846	T20847	compound	animal,models
R5908	T20847	T20845	pobj	models,of
R5909	T20848	T20847	prep	of,models
R5910	T20896	T20892	auxpass	is,expected
R5911	T20897	T20898	aux	to,advance
R5912	T20849	T20850	amod	genetic,diseases
R5913	T20898	T20892	xcomp	advance,expected
R5914	T20899	T20900	amod	such,approaches
R5915	T20900	T20898	dobj	approaches,advance
R5916	T20850	T20848	pobj	diseases,of
R5917	T20901	T20900	amod	therapeutic,approaches
R5918	T20902	T20892	cc	and,expected
R5919	T20903	T20904	aux	could,pave
R5920	T20904	T20892	conj	pave,expected
R5921	T20851	T20841	prep	for,importance
R5922	T20905	T20906	det	the,way
R5923	T20906	T20904	dobj	way,pave
R5924	T20852	T20853	amod	preclinical,studies
R5925	T20907	T20904	prep	for,pave
R5926	T20908	T20907	pobj	studies,for
R5927	T20853	T20851	pobj	studies,for
R5928	T20909	T20908	prep	in,studies
R5929	T20910	T20909	pobj	humans,in
R5930	T20911	T20892	punct	.,expected
R5931	T20854	T20828	punct	.,highlight
R5932	T20913	T20914	prep	In,be
R5933	T20856	T20857	det	The,testing
R5934	T20857	T20858	nsubj	testing,provides
R5935	T20915	T20913	pobj	addition,In
R5936	T20916	T20915	prep	to,addition
R5937	T20859	T20857	prep	of,testing
R5938	T20917	T20916	pcomp	testing,to
R5939	T20918	T20919	amod	various,treatments
R5940	T20919	T20917	dobj	treatments,testing
R5941	T20920	T20914	punct	", ",be
R5942	T20860	T20861	npadvmod	gene,based
R5943	T20921	T20922	det	these,models
R5944	T20922	T20914	nsubj	models,be
R5945	T20923	T20914	aux	should,be
R5946	T20861	T20864	amod	based,therapies
R5947	T20924	T20914	advmod	also,be
R5948	T20925	T20926	advmod	very,useful
R5949	T20862	T20860	cc	and,gene
R5950	T20926	T20914	acomp	useful,be
R5951	T20927	T20926	prep	for,useful
R5952	T20863	T20860	conj	cell,gene
R5953	T20928	T20927	pcomp	investigating,for
R5954	T20929	T20930	det	the,consequences
R5955	T20930	T20928	dobj	consequences,investigating
R5956	T20931	T20930	amod	underlying,consequences
R5957	T20932	T20930	amod	pathophysiologic,consequences
R5958	T20933	T20930	prep	of,consequences
R5959	T20864	T20859	pobj	therapies,of
R5960	T20934	T20935	det	the,disease
R5961	T20935	T20933	pobj	disease,of
R5962	T20936	T20914	punct	.,be
R5963	T20865	T20857	prep	on,testing
R5964	T20938	T20939	amod	Such,studies
R5965	T20939	T20940	nsubj	studies,are
R5966	T20866	T20867	amod	appropriate,systems
R5967	T20941	T20942	advmod	very,difficult
R5968	T20942	T20943	amod	difficult,impossible
R5969	T20867	T20865	pobj	systems,on
R5970	T20943	T20940	acomp	impossible,are
R5971	T20944	T20943	punct	/,impossible
R5972	T20945	T20946	aux	to,do
R5973	T20868	T20867	compound	animal,systems
R5974	T20946	T20943	advcl	do,impossible
R5975	T20947	T20946	prep	in,do
R5976	T20948	T20949	amod	human,patients
R5977	T20869	T20867	compound	model,systems
R5978	T20949	T20947	pobj	patients,in
R5979	T20950	T20946	prep	for,do
R5980	T20951	T20952	amod	obvious,reasons
R5981	T20870	T20871	det	a,method
R5982	T20952	T20950	pobj	reasons,for
R5983	T20953	T20952	amod	ethical,reasons
R5984	T20954	T20940	punct	", ",are
R5985	T20871	T20858	dobj	method,provides
R5986	T20955	T20940	cc	and,are
R5987	T20956	T20957	advmod	often,rely
R5988	T20957	T20940	conj	rely,are
R5989	T20872	T20871	amod	preliminary,method
R5990	T20958	T20957	aux	must,rely
R5991	T20959	T20957	prep	on,rely
R5992	T20960	T20961	compound	autopsy,tissue
R5993	T20873	T20871	prep	of,method
R5994	T20961	T20959	pobj	tissue,on
R5995	T20962	T20940	punct	.,are
R5996	T20874	T20873	pcomp	establishing,of
R5997	T20964	T20965	advmod	Additionally,be
R5998	T20875	T20876	preconj	not,efficacy
R5999	T20966	T20965	punct	", ",be
R6000	T20967	T20968	det	the,model
R6001	T20968	T20965	nsubj	model,be
R6002	T20969	T20968	amod	intermediate,model
R6003	T20876	T20874	dobj	efficacy,establishing
R6004	T20970	T20968	compound	MSUD,model
R6005	T20971	T20965	aux	may,be
R6006	T20877	T20875	advmod	only,not
R6007	T20972	T20965	advmod	also,be
R6008	T20973	T20965	acomp	useful,be
R6009	T20974	T20973	prep	for,useful
R6010	T20975	T20974	pobj	studies,for
R6011	T20976	T20977	aux	to,test
R6012	T20977	T20975	advcl	test,studies
R6013	T20878	T20876	det	the,efficacy
R6014	T20978	T20979	det	the,effect
R6015	T20979	T20977	dobj	effect,test
R6016	T20980	T20979	prep	of,effect
R6017	T20879	T20876	punct	", ",efficacy
R6018	T20981	T20980	pobj	thiamin,of
R6019	T20982	T20965	punct	.,be
R6020	T20880	T20876	cc	but,efficacy
R6021	T20984	T20985	det	A,form
R6022	T20881	T20880	advmod	also,but
R6023	T20985	T20989	nsubjpass	form,described
R6024	T20882	T20883	amod	short,term
R6025	T20986	T20987	npadvmod	thiamin,responsive
R6026	T20987	T20985	amod	responsive,form
R6027	T20883	T20888	compound	term,safety
R6028	T20988	T20987	punct	-,responsive
R6029	T20990	T20985	prep	of,form
R6030	T20884	T20882	punct	-,short
R6031	T20991	T20990	pobj	MSUD,of
R6032	T20992	T20989	aux	has,described
R6033	T20885	T20882	cc	and,short
R6034	T20993	T20989	auxpass	been,described
R6035	T20994	T20995	punct	[,1
R6036	T20886	T20882	conj	long,short
R6037	T20995	T20989	parataxis	1,described
R6038	T20996	T20995	punct	],1
R6039	T20997	T20989	punct	.,described
R6040	T20887	T20883	punct	-,term
R6041	T20999	T21000	det	The,phenotype
R6042	T21000	T21001	nsubj	phenotype,is
R6043	T20888	T20876	conj	safety,efficacy
R6044	T20889	T20858	punct	.,provides
R6045	T20891	T20892	nsubjpass	Success,expected
R6046	T20893	T20891	prep	with,Success
R6047	T21002	T21000	prep	of,phenotype
R6048	T21003	T21004	det	these,patients
R6049	T20894	T20895	compound	animal,studies
R6050	T21004	T21002	pobj	patients,of
R6051	T20895	T20893	pobj	studies,with
R6052	T21005	T21001	acomp	heterogeneous,is
R6053	T21006	T21001	cc	and,is
R6055	T21007	T21008	nsubj	treatment,produced
R6056	T21008	T21001	conj	produced,is
R6057	T21009	T21007	prep	with,treatment
R6058	T21010	T21011	det	a,range
R6059	T21011	T21009	pobj	range,with
R6060	T21012	T21011	amod	wide,range
R6061	T21013	T21011	prep	of,range
R6062	T21014	T21015	compound	thiamin,doses
R6064	T21015	T21013	pobj	doses,of
R6065	T21016	T21008	aux	has,produced
R6066	T21017	T21018	amod	limited,success
R6067	T21018	T21008	dobj	success,produced
R6069	T21019	T21020	punct	[,1
R6070	T21020	T21008	parataxis	1,produced
R6072	T21021	T21020	punct	],1
R6073	T21022	T21008	punct	.,produced
R6075	T21024	T21025	amod	Recent,studies
R6076	T21025	T21028	nsubj	studies,suggested
R6077	T21026	T21027	compound	cell,culture
R6079	T21027	T21025	compound	culture,studies
R6080	T21029	T21025	prep	with,studies
R6082	T21030	T21031	compound	MSUD,cells
R6083	T21031	T21029	pobj	cells,with
R6084	T21032	T21028	aux	have,suggested
R6086	T21033	T21034	mark	that,is
R6087	T21034	T21028	ccomp	is,suggested
R6089	T21035	T21036	det	the,phenotype
R6090	T21036	T21034	nsubj	phenotype,is
R6091	T21117	T21098	punct	", ",provide
R6092	T21037	T21038	npadvmod	thiamin,responsive
R6093	T21038	T21036	amod	responsive,phenotype
R6094	T21118	T21119	det	the,model
R6095	T21039	T21038	punct	-,responsive
R6096	T21040	T21034	acomp	dependent,is
R6097	T21041	T21040	prep	upon,dependent
R6098	T21119	T21098	nsubj	model,provide
R6099	T21042	T21043	det	the,presence
R6100	T21043	T21041	pobj	presence,upon
R6101	T21044	T21043	prep	of,presence
R6102	T21045	T21046	advmod	at,one
R6103	T21120	T21119	amod	intermediate,model
R6104	T21046	T21048	nummod	one,allele
R6105	T21047	T21046	advmod	least,one
R6106	T21048	T21044	pobj	allele,of
R6107	T21121	T21119	compound	MSUD,model
R6108	T21049	T21050	npadvmod	E2,expressing
R6109	T21050	T21048	amod	expressing,allele
R6110	T21051	T21052	punct	[,46
R6111	T21052	T21028	parataxis	46,suggested
R6112	T21053	T21052	nummod	45,46
R6113	T21054	T21052	punct	",",46
R6114	T21055	T21052	punct	],46
R6115	T21122	T21098	aux	may,provide
R6116	T21056	T21028	punct	.,suggested
R6117	T21058	T21059	prep	In,provides
R6118	T21123	T21124	det	a,resource
R6119	T21060	T21058	pobj	light,In
R6120	T21061	T21060	prep	of,light
R6121	T21124	T21098	dobj	resource,provide
R6122	T21062	T21063	det	these,findings
R6123	T21063	T21061	pobj	findings,of
R6124	T21064	T21063	amod	newer,findings
R6125	T21125	T21124	amod	valuable,resource
R6126	T21065	T21059	punct	", ",provides
R6127	T21066	T21067	poss	our,mouse
R6128	T21126	T21124	prep	for,resource
R6129	T21067	T21059	nsubj	mouse,provides
R6130	T21068	T21067	amod	intermediate,mouse
R6131	T21069	T21067	compound	MSUD,mouse
R6132	T21127	T21126	pobj	studies,for
R6133	T21070	T21071	det	a,model
R6134	T21071	T21059	dobj	model,provides
R6135	T21072	T21073	aux	to,test
R6136	T21073	T21071	advcl	test,model
R6137	T21128	T21127	prep	of,studies
R6138	T21074	T21075	det	the,effect
R6139	T21075	T21073	dobj	effect,test
R6140	T21076	T21075	prep	of,effect
R6141	T21129	T21130	amod	structural,biology
R6142	T21077	T21076	pobj	thiamin,of
R6143	T21130	T21128	pobj	biology,of
R6144	T21078	T21073	prep	with,test
R6145	T21079	T21078	pobj	respect,with
R6146	T21080	T21079	prep	to,respect
R6147	T21081	T21082	compound	BCKDH,activity
R6148	T21131	T21098	punct	.,provide
R6149	T21082	T21080	pobj	activity,to
R6150	T21083	T21082	cc	and,activity
R6151	T21084	T21085	compound	blood,levels
R6152	T21133	T21134	advmod	Lastly,be
R6153	T21085	T21082	conj	levels,activity
R6154	T21086	T21087	compound	amino,acid
R6155	T21087	T21085	compound	acid,levels
R6156	T21088	T21073	prep	at,test
R6157	T21135	T21134	punct	", ",be
R6158	T21089	T21090	det	the,level
R6159	T21090	T21088	pobj	level,at
R6160	T21136	T21137	det	the,information
R6161	T21091	T21090	prep	of,level
R6162	T21092	T21093	det	the,animal
R6163	T21093	T21091	pobj	animal,of
R6164	T21094	T21093	amod	whole,animal
R6165	T21095	T21059	punct	.,provides
R6166	T21137	T21134	nsubj	information,be
R6167	T21097	T21098	prep	Because,provide
R6168	T21138	T21137	cc	and,information
R6169	T21099	T21097	pcomp	of,Because
R6170	T21100	T21101	amod	recent,interest
R6171	T21101	T21097	pobj	interest,Because
R6172	T21139	T21137	conj	knowledge,information
R6173	T21102	T21101	prep	in,interest
R6174	T21103	T21104	amod	structural,analysis
R6175	T21104	T21102	pobj	analysis,in
R6176	T21140	T21137	acl	gained,information
R6177	T21105	T21104	prep	of,analysis
R6178	T21106	T21107	compound	multienzyme,complexes
R6179	T21107	T21105	pobj	complexes,of
R6180	T21141	T21140	prep	from,gained
R6181	T21142	T21141	pobj	studies,from
R6182	T21143	T21142	prep	with,studies
R6183	T21144	T21145	det	the,models
R6184	T21145	T21143	pobj	models,with
R6185	T21146	T21145	compound	MSUD,models
R6186	T21147	T21145	acl	described,models
R6187	T21148	T21147	advmod	here,described
R6188	T21149	T21134	aux	will,be
R6189	T21150	T21134	advmod	also,be
R6190	T21151	T21134	acomp	applicable,be
R6191	T21152	T21151	cc	and,applicable
R6192	T21153	T21151	conj	transferable,applicable
R6193	T21154	T21153	prep	to,transferable
R6194	T21155	T21156	amod	other,disorders
R6195	T21156	T21154	pobj	disorders,to
R6196	T21157	T21156	amod	mitochondrial,disorders
R6197	T21158	T21134	prep	due,be
R6198	T21159	T21158	pcomp	to,due
R6199	T21160	T21158	pobj	defects,due
R6200	T21161	T21160	prep	in,defects
R6201	T21162	T21163	amod	multisubunit,enzymes
R6202	T21163	T21161	pobj	enzymes,in
R6203	T21164	T21134	punct	.,be
R6204	T21291	T21292	prep	In,describes
R6205	T21293	T21291	pobj	summary,In
R6206	T21294	T21292	punct	", ",describes
R6207	T21295	T21296	det	this,report
R6208	T21296	T21292	nsubj	report,describes
R6209	T21297	T21298	det	the,development
R6210	T21298	T21292	dobj	development,describes
R6211	T21299	T21298	cc	and,development
R6212	T21300	T21298	conj	characterization,development
R6213	T21301	T21298	prep	of,development
R6214	T21302	T21303	advmod	genetically,engineered
R6215	T21303	T21304	amod	engineered,models
R6216	T21304	T21301	pobj	models,of
R6217	T21305	T21304	compound	mouse,models
R6218	T21306	T21304	prep	of,models
R6219	T21307	T21308	amod	classic,MSUD
R6220	T21308	T21306	pobj	MSUD,of
R6221	T21309	T21310	advmod	as,as
R6222	T21310	T21307	cc	as,classic
R6223	T21311	T21310	advmod	well,as
R6224	T21312	T21307	conj	intermediate,classic
R6225	T21313	T21292	punct	.,describes
R6226	T21315	T21316	det	These,animals
R6227	T21316	T21317	nsubj	animals,provide
R6228	T21318	T21319	amod	useful,models
R6229	T21319	T21317	dobj	models,provide
R6230	T21320	T21321	aux	to,characterize
R6231	T21321	T21319	advcl	characterize,models
R6232	T21322	T21321	advmod	further,characterize
R6233	T21323	T21324	det	the,pathogenesis
R6234	T21324	T21321	dobj	pathogenesis,characterize
R6235	T21325	T21324	prep	of,pathogenesis
R6236	T21326	T21325	pobj	MSUD,of
R6237	T21327	T21317	punct	", ",provide
R6238	T21328	T21329	advmod	as,as
R6239	T21329	T21317	cc	as,provide
R6240	T21330	T21329	advmod	well,as
R6241	T21331	T21317	conj	models,provide
R6242	T21332	T21333	aux	to,test
R6243	T21333	T21331	advcl	test,models
R6244	T21334	T21335	amod	novel,strategies
R6245	T21335	T21333	dobj	strategies,test
R6246	T21336	T21335	amod	therapeutic,strategies
R6247	T21337	T21335	punct	", ",strategies
R6248	T21338	T21339	amod	such,as
R6249	T21339	T21335	prep	as,strategies
R6250	T21340	T21341	nmod	gene,therapies
R6251	T21341	T21339	pobj	therapies,as
R6252	T21342	T21340	cc	and,gene
R6253	T21343	T21340	conj	cellular,gene
R6254	T21344	T21333	punct	", ",test
R6255	T21345	T21346	aux	to,treat
R6256	T21346	T21333	advcl	treat,test
R6257	T21347	T21348	det	this,disease
R6258	T21348	T21346	dobj	disease,treat
R6259	T21349	T21348	amod	devastating,disease
R6260	T21350	T21348	amod	metabolic,disease
R6261	T21351	T21317	punct	.,provide
R6262	T21373	T21374	det	The,history
R6263	T21374	T21376	nsubjpass	history,accessed
R6264	T21375	T21374	amod	pre-publication,history
R6265	T21377	T21374	prep	for,history
R6266	T21378	T21379	det	this,paper
R6267	T21379	T21377	pobj	paper,for
R6268	T21380	T21376	aux	can,accessed
R6269	T21381	T21376	auxpass	be,accessed
R6270	T21382	T21376	advmod	here,accessed
R6271	T21383	T21376	punct	:,accessed
R6272	T22055	T22056	compound	E2,production
R6273	T22057	T22058	compound	gene,knockout
R6274	T22058	T22056	compound	knockout,production
R6275	T22059	T22056	compound	mouse,production
R6276	T22060	T22056	punct	.,production
R6277	T22062	T22063	meta	A,strategy
R6278	T22064	T22063	punct	", ",strategy
R6279	T22065	T22066	compound	Gene,targeting
R6280	T22066	T22063	compound	targeting,strategy
R6281	T22067	T22063	acl	used,strategy
R6282	T22068	T22067	prep	for,used
R6283	T22069	T22068	pcomp	targeting,for
R6284	T22070	T22071	det	the,locus
R6285	T22071	T22069	dobj	locus,targeting
R6286	T22072	T22071	compound	E2,locus
R6287	T22073	T22067	prep	in,used
R6288	T22074	T22075	compound	mouse,cells
R6289	T22075	T22073	pobj	cells,in
R6290	T22076	T22075	compound	ES,cells
R6291	T22077	T22063	punct	.,strategy
R6292	T22079	T22080	det	The,construct
R6293	T22080	T22082	nsubjpass	construct,designed
R6294	T22081	T22080	compound	targeting,construct
R6295	T22083	T22082	auxpass	was,designed
R6296	T22084	T22085	aux	to,delete
R6297	T22085	T22082	advcl	delete,designed
R6298	T22086	T22087	nummod	1.67,kb
R6299	T22087	T22085	dobj	kb,delete
R6300	T22088	T22087	prep	of,kb
R6301	T22089	T22088	pobj	sequence,of
R6302	T22090	T22085	prep	between,delete
R6303	T22091	T22092	det	an,site
R6304	T22092	T22090	pobj	site,between
R6305	T22093	T22092	compound	EcoRV,site
R6306	T22094	T22092	prep	in,site
R6307	T22095	T22094	pobj	Exon,in
R6308	T22096	T22095	nummod	4,Exon
R6309	T22097	T22092	cc	and,site
R6310	T22098	T22099	det	a,site
R6311	T22099	T22092	conj	site,site
R6312	T22100	T22099	compound	Smal,site
R6313	T22101	T22099	prep	in,site
R6314	T22102	T22101	pobj	intron,in
R6315	T22103	T22102	nummod	5,intron
R6316	T22104	T22082	punct	.,designed
R6317	T22106	T22107	det	The,gene
R6318	T22107	T22111	nsubj	gene,contains
R6319	T22108	T22109	amod	wild,type
R6320	T22109	T22107	compound	type,gene
R6321	T22110	T22107	compound	E2,gene
R6322	T22112	T22113	det	an,fragment
R6323	T22113	T22111	dobj	fragment,contains
R6324	T22114	T22115	punct	~,16
R6325	T22115	T22116	nummod	16,kb
R6326	T22116	T22113	compound	kb,fragment
R6327	T22117	T22113	compound	BglI,fragment
R6328	T22118	T22113	compound	restriction,fragment
R6329	T22119	T22120	dep	that,hybridizes
R6330	T22120	T22113	relcl	hybridizes,fragment
R6331	T22121	T22120	prep	to,hybridizes
R6332	T22122	T22123	det	the,probe
R6333	T22123	T22121	pobj	probe,to
R6334	T22124	T22125	npadvmod	Exon,specific
R6335	T22125	T22123	amod	specific,probe
R6336	T22126	T22124	nummod	6,Exon
R6337	T22127	T22111	punct	.,contains
R6338	T22129	T22130	det	A,locus
R6339	T22130	T22134	nsubj	locus,harbors
R6340	T22131	T22132	advmod	correctly,targeted
R6341	T22132	T22130	amod	targeted,locus
R6342	T22133	T22130	compound	E2,locus
R6343	T22135	T22136	det	an,fragment
R6344	T22136	T22134	dobj	fragment,harbors
R6345	T22137	T22138	punct	~,11
R6346	T22138	T22139	nummod	11,kb
R6347	T22139	T22136	compound	kb,fragment
R6348	T22140	T22136	compound	BglI,fragment
R6349	T22141	T22136	compound	restriction,fragment
R6350	T22142	T22143	dep	that,hybridizes
R6351	T22143	T22136	relcl	hybridizes,fragment
R6352	T22144	T22143	prep	to,hybridizes
R6353	T22145	T22146	det	the,probe
R6354	T22146	T22144	pobj	probe,to
R6355	T22147	T22146	amod	same,probe
R6356	T22148	T22134	punct	.,harbors
R6357	T22151	T22152	mark	that,detect
R6358	T22152	T22150	ccomp	detect,Note
R6359	T22153	T22154	det	the,probe
R6360	T22154	T22152	nsubj	probe,detect
R6361	T22155	T22152	aux	will,detect
R6362	T22156	T22152	neg	not,detect
R6363	T22157	T22158	amod	random,integration
R6364	T22158	T22152	dobj	integration,detect
R6365	T22159	T22158	prep	of,integration
R6366	T22160	T22161	det	the,vector
R6367	T22161	T22159	pobj	vector,of
R6368	T22162	T22161	compound	targeting,vector
R6369	T22163	T22164	mark	because,is
R6370	T22164	T22152	advcl	is,detect
R6371	T22165	T22164	nsubj	it,is
R6372	T22166	T22164	acomp	external,is
R6373	T22167	T22166	prep	to,external
R6374	T22168	T22169	det	the,vector
R6375	T22169	T22167	pobj	vector,to
R6376	T22170	T22169	compound	targeting,vector
R6377	T22171	T22150	punct	.,Note
R6378	T22173	T22174	meta	B,analysis
R6379	T22175	T22174	punct	", ",analysis
R6380	T22176	T22177	compound	Southern,blot
R6381	T22177	T22174	compound	blot,analysis
R6382	T22178	T22174	prep	of,analysis
R6383	T22179	T22180	npadvmod	Bgll,digested
R6384	T22180	T22181	amod	digested,DNA
R6385	T22181	T22178	pobj	DNA,of
R6386	T22182	T22181	amod	genomic,DNA
R6387	T22183	T22181	acl	derived,DNA
R6388	T22184	T22183	prep	from,derived
R6389	T22185	T22186	det	the,line
R6390	T22186	T22184	pobj	line,from
R6391	T22187	T22186	amod	parental,line
R6392	T22188	T22189	amod	wild,type
R6393	T22189	T22186	compound	type,line
R6394	T22190	T22191	compound	ES,cell
R6395	T22191	T22186	compound	cell,line
R6396	T22192	T22193	punct	(,R1
R6397	T22193	T22186	parataxis	R1,line
R6398	T22194	T22193	punct	),R1
R6399	T22195	T22186	punct	", ",line
R6400	T22196	T22197	det	a,line
R6401	T22197	T22186	appos	line,line
R6402	T22198	T22197	amod	heterozygous,line
R6403	T22199	T22197	amod	targeted,line
R6404	T22200	T22201	compound	ES,cell
R6405	T22201	T22197	compound	cell,line
R6406	T22202	T22203	punct	(,362
R6407	T22203	T22197	parataxis	362,line
R6408	T22204	T22203	punct	),362
R6409	T22205	T22184	punct	", ",from
R6410	T22206	T22184	cc	and,from
R6411	T22207	T22184	conj	from,from
R6412	T22208	T22209	amod	wild,type
R6413	T22209	T22210	nmod	type,knockout
R6414	T22210	T22225	nmod	knockout,mice
R6415	T22211	T22212	punct	(,+
R6416	T22212	T22209	punct	+,type
R6417	T22213	T22212	punct	+,+
R6418	T22214	T22212	punct	/,+
R6419	T22215	T22212	punct	),+
R6420	T22216	T22209	punct	", ",type
R6421	T22217	T22209	conj	heterozygous,type
R6422	T22218	T22219	punct	(,-
R6423	T22219	T22217	punct	-,heterozygous
R6424	T22220	T22219	punct	+,-
R6425	T22221	T22219	punct	/,-
R6426	T22222	T22219	punct	),-
R6427	T22223	T22217	cc	and,heterozygous
R6428	T22224	T22217	conj	homozygous,heterozygous
R6429	T22225	T22207	pobj	mice,from
R6430	T22226	T22227	punct	(,-
R6431	T22227	T22210	punct	-,knockout
R6432	T22228	T22227	punct	-,-
R6433	T22229	T22227	punct	/,-
R6434	T22230	T22227	punct	),-
R6435	T22231	T22174	punct	.,analysis
R6436	T22233	T22234	det	The,blot
R6437	T22234	T22235	nsubjpass	blot,hybridized
R6438	T22236	T22235	auxpass	was,hybridized
R6439	T22237	T22235	prep	with,hybridized
R6440	T22238	T22239	det	an,probe
R6441	T22239	T22237	pobj	probe,with
R6442	T22240	T22241	npadvmod	Exon,specific
R6443	T22241	T22239	amod	specific,probe
R6444	T22242	T22240	nummod	6,Exon
R6445	T22243	T22235	punct	.,hybridized
R6446	T22245	T22246	meta	C,analysis
R6447	T22247	T22246	punct	", ",analysis
R6448	T22248	T22246	amod	Immunohistochemical,analysis
R6449	T22249	T22246	prep	of,analysis
R6450	T22250	T22251	amod	fresh,frozen
R6451	T22251	T22252	amod	frozen,sections
R6452	T22252	T22249	pobj	sections,of
R6453	T22253	T22252	compound	liver,sections
R6454	T22254	T22252	prep	from,sections
R6455	T22255	T22256	nmod	control,knockout
R6456	T22256	T22264	nmod	knockout,pups
R6457	T22257	T22258	punct	(,+
R6458	T22258	T22255	punct	+,control
R6459	T22259	T22258	punct	+,+
R6460	T22260	T22258	punct	/,+
R6461	T22261	T22258	punct	),+
R6462	T22262	T22255	cc	and,control
R6463	T22263	T22255	conj	E2,control
R6464	T22264	T22254	pobj	pups,from
R6465	T22265	T22266	punct	(,-
R6466	T22266	T22256	punct	-,knockout
R6467	T22267	T22266	punct	-,-
R6468	T22268	T22266	punct	/,-
R6469	T22269	T22266	punct	),-
R6470	T22270	T22271	amod	postnatal,day
R6471	T22271	T22264	nmod	day,pups
R6472	T22272	T22271	nummod	1,day
R6473	T22273	T22264	compound	mouse,pups
R6474	T22274	T22246	punct	.,analysis
R6475	T22276	T22277	nsubjpass	Sections,stained
R6476	T22278	T22277	auxpass	were,stained
R6477	T22279	T22277	prep	for,stained
R6478	T22280	T22279	pobj	E2,for
R6479	T22281	T22277	advcl	using,stained
R6480	T22282	T22283	det	an,antibody
R6481	T22283	T22281	dobj	antibody,using
R6482	T22284	T22285	npadvmod	E2,specific
R6483	T22285	T22283	amod	specific,antibody
R6484	T22286	T22287	punct	(,green
R6485	T22287	T22283	parataxis	green,antibody
R6486	T22288	T22287	punct	),green
R6487	T22289	T22283	cc	and,antibody
R6488	T22290	T22291	det	a,stain
R6489	T22291	T22283	conj	stain,antibody
R6490	T22292	T22291	amod	nuclear,stain
R6491	T22293	T22294	punct	(,blue
R6492	T22294	T22291	parataxis	blue,stain
R6493	T22295	T22294	punct	),blue
R6494	T22296	T22277	punct	.,stained
R6495	T22299	T22300	det	the,absence
R6496	T22300	T22298	dobj	absence,Note
R6497	T22301	T22300	amod	complete,absence
R6498	T22302	T22300	prep	of,absence
R6499	T22303	T22304	compound	E2,immunoreactivity
R6500	T22304	T22302	pobj	immunoreactivity,of
R6501	T22305	T22298	prep	in,Note
R6502	T22306	T22307	det	the,section
R6503	T22307	T22305	pobj	section,in
R6504	T22308	T22307	prep	from,section
R6505	T22309	T22310	det	the,mouse
R6506	T22310	T22308	pobj	mouse,from
R6507	T22311	T22310	compound	knockout,mouse
R6508	T22312	T22298	punct	.,Note
R6509	T22314	T22315	meta	D,observed
R6510	T22316	T22315	punct	", ",observed
R6511	T22317	T22318	amod	Similar,results
R6512	T22318	T22315	nsubjpass	results,observed
R6513	T22319	T22315	auxpass	were,observed
R6514	T22320	T22315	prep	upon,observed
R6515	T22321	T22322	amod	immunohistochemical,analysis
R6516	T22322	T22320	pobj	analysis,upon
R6517	T22323	T22322	prep	of,analysis
R6518	T22324	T22325	amod	primary,fibroblasts
R6519	T22325	T22323	pobj	fibroblasts,of
R6520	T22326	T22325	nmod	mouse,fibroblasts
R6521	T22327	T22325	amod	embryonic,fibroblasts
R6522	T22328	T22325	punct	(,fibroblasts
R6523	T22329	T22325	appos	MEFs,fibroblasts
R6524	T22330	T22315	punct	),observed
R6525	T22331	T22315	punct	.,observed
R6526	T22334	T22335	mark	that,was
R6527	T22335	T22333	ccomp	was,Note
R6528	T22336	T22337	det	the,signal
R6529	T22337	T22335	nsubj	signal,was
R6530	T22338	T22339	advmod	readily,detectable
R6531	T22339	T22337	amod	detectable,signal
R6532	T22340	T22337	prep	for,signal
R6533	T22341	T22340	pobj	E2,for
R6534	T22342	T22337	prep	in,signal
R6535	T22343	T22344	det	the,cells
R6536	T22344	T22342	pobj	cells,in
R6537	T22345	T22344	compound	control,cells
R6538	T22346	T22335	acomp	present,was
R6539	T22347	T22346	prep	in,present
R6540	T22348	T22349	det	a,pattern
R6541	T22349	T22347	pobj	pattern,in
R6542	T22350	T22349	amod	characteristic,pattern
R6543	T22351	T22350	prep	of,characteristic
R6544	T22352	T22351	pobj	mitochondria,of
R6545	T22353	T22352	punct	", ",mitochondria
R6546	T22354	T22355	det	the,location
R6547	T22355	T22352	appos	location,mitochondria
R6548	T22356	T22355	amod	subcellular,location
R6549	T22357	T22355	prep	of,location
R6550	T22358	T22357	pobj	BCKDH,of
R6551	T22359	T22333	punct	.,Note
R6552	T22807	T22808	amod	Biochemical,characterization
R6553	T22809	T22808	prep	of,characterization
R6554	T22810	T22811	det	the,model
R6555	T22811	T22809	pobj	model,of
R6556	T22812	T22811	amod	classic,model
R6557	T22813	T22811	nmod	MSUD,model
R6558	T22814	T22811	amod	murine,model
R6559	T22815	T22808	punct	.,characterization
R6560	T22817	T22818	meta	A,activity
R6561	T22819	T22818	punct	", ",activity
R6562	T22820	T22818	compound	BCKDH,activity
R6563	T22821	T22818	compound	enzyme,activity
R6564	T22822	T22818	prep	in,activity
R6565	T22823	T22822	pobj	liver,in
R6566	T22824	T22823	prep	of,liver
R6567	T22825	T22826	amod	newborn,mice
R6568	T22826	T22824	pobj	mice,of
R6569	T22827	T22828	amod	wild,type
R6570	T22828	T22829	nmod	type,control
R6571	T22829	T22830	nmod	control,knockout
R6572	T22830	T22826	compound	knockout,mice
R6573	T22831	T22832	punct	(,+
R6574	T22832	T22829	punct	+,control
R6575	T22833	T22832	punct	+,+
R6576	T22834	T22832	punct	/,+
R6577	T22835	T22832	punct	),+
R6578	T22836	T22829	punct	", ",control
R6579	T22837	T22829	conj	heterozygous,control
R6580	T22838	T22839	punct	(,-
R6581	T22839	T22837	punct	-,heterozygous
R6582	T22840	T22839	punct	+,-
R6583	T22841	T22839	punct	/,-
R6584	T22842	T22839	punct	),-
R6585	T22843	T22837	punct	", ",heterozygous
R6586	T22844	T22837	cc	and,heterozygous
R6587	T22845	T22837	conj	homozygous,heterozygous
R6588	T22846	T22847	punct	(,-
R6589	T22847	T22845	punct	-,homozygous
R6590	T22848	T22847	punct	-,-
R6591	T22849	T22847	punct	/,-
R6592	T22850	T22847	punct	),-
R6593	T22851	T22818	punct	.,activity
R6594	T22853	T22854	compound	Enzyme,activity
R6595	T22854	T22855	nsubj	activity,was
R6596	T22856	T22857	advmod	significantly,reduced
R6597	T22857	T22855	acomp	reduced,was
R6598	T22858	T22855	prep	in,was
R6599	T22859	T22860	punct	+,-
R6600	T22860	T22862	punct	-,liver
R6601	T22861	T22860	punct	/,-
R6602	T22862	T22858	pobj	liver,in
R6603	T22863	T22855	prep	compared,was
R6604	T22864	T22863	prep	to,compared
R6605	T22865	T22866	punct	+,+
R6606	T22866	T22864	punct	+,to
R6607	T22867	T22866	punct	/,+
R6608	T22868	T22855	punct	", ",was
R6609	T22869	T22855	cc	and,was
R6610	T22870	T22855	conj	was,was
R6611	T22871	T22870	prep	below,was
R6612	T22872	T22873	det	the,level
R6613	T22873	T22871	pobj	level,below
R6614	T22874	T22873	prep	of,level
R6615	T22875	T22874	pobj	detection,of
R6616	T22876	T22870	prep	in,was
R6617	T22877	T22878	punct	-,-
R6618	T22878	T22880	punct	-,liver
R6619	T22879	T22878	punct	/,-
R6620	T22880	T22876	pobj	liver,in
R6621	T22881	T22855	punct	.,was
R6622	T22883	T22884	meta	B,concentrations
R6623	T22885	T22884	punct	", ",concentrations
R6624	T22886	T22884	amod	Total,concentrations
R6625	T22887	T22884	compound	BCAA,concentrations
R6626	T22888	T22884	prep	in,concentrations
R6627	T22889	T22888	pobj	blood,in
R6628	T22890	T22889	prep	of,blood
R6629	T22891	T22890	pobj	mice,of
R6630	T22892	T22884	punct	.,concentrations
R6631	T22894	T22895	amod	Total,BCAA
R6632	T22895	T22896	nsubj	BCAA,represent
R6633	T22897	T22898	det	the,sum
R6634	T22898	T22896	dobj	sum,represent
R6635	T22899	T22898	prep	of,sum
R6636	T22900	T22899	pobj	leucine,of
R6637	T22901	T22900	punct	", ",leucine
R6638	T22902	T22900	conj	isoleucine,leucine
R6639	T22903	T22902	punct	", ",isoleucine
R6640	T22904	T22902	cc	and,isoleucine
R6641	T22905	T22902	conj	valine,isoleucine
R6642	T22906	T22896	punct	.,represent
R6643	T22908	T22909	amod	Total,concentrations
R6644	T22909	T22911	nsubj	concentrations,were
R6645	T22910	T22909	compound	BCAA,concentrations
R6646	T22912	T22909	prep	in,concentrations
R6647	T22913	T22912	pobj	blood,in
R6648	T22914	T22913	prep	from,blood
R6649	T22915	T22916	punct	-,-
R6650	T22916	T22918	punct	-,mice
R6651	T22917	T22916	punct	/,-
R6652	T22918	T22914	pobj	mice,from
R6653	T22919	T22920	advmod	significantly,elevated
R6654	T22920	T22911	acomp	elevated,were
R6655	T22921	T22911	prep	compared,were
R6656	T22922	T22921	prep	to,compared
R6657	T22923	T22924	punct	+,+
R6658	T22924	T22922	punct	+,to
R6659	T22925	T22924	punct	/,+
R6660	T22926	T22924	cc	and,+
R6661	T22927	T22928	punct	+,-
R6662	T22928	T22924	conj	-,+
R6663	T22929	T22928	punct	/,-
R6664	T22930	T22911	punct	.,were
R6665	T22932	T22933	meta	C,Ratio
R6666	T22934	T22933	punct	", ",Ratio
R6667	T22935	T22933	prep	of,Ratio
R6668	T22936	T22937	amod	total,BCAA
R6669	T22937	T22935	pobj	BCAA,of
R6670	T22938	T22933	prep	to,Ratio
R6671	T22939	T22938	pobj	alanine,to
R6672	T22940	T22933	prep	in,Ratio
R6673	T22941	T22940	pobj	blood,in
R6674	T22942	T22941	prep	of,blood
R6675	T22943	T22942	pobj	mice,of
R6676	T22944	T22933	punct	.,Ratio
R6677	T22946	T22947	det	This,ratio
R6678	T22947	T22948	nsubj	ratio,was
R6679	T22949	T22950	advmod	significantly,elevated
R6680	T22950	T22948	acomp	elevated,was
R6681	T22951	T22948	prep	in,was
R6682	T22952	T22953	punct	-,-
R6683	T22953	T22955	punct	-,mice
R6684	T22954	T22953	punct	/,-
R6685	T22955	T22951	pobj	mice,in
R6686	T22956	T22948	prep	compared,was
R6687	T22957	T22956	prep	to,compared
R6688	T22958	T22959	punct	+,+
R6689	T22959	T22961	punct	+,mice
R6690	T22960	T22959	punct	/,+
R6691	T22961	T22957	pobj	mice,to
R6692	T22962	T22959	cc	and,+
R6693	T22963	T22964	punct	+,-
R6694	T22964	T22959	conj	-,+
R6695	T22965	T22964	punct	/,-
R6696	T22966	T22948	punct	.,was
R6697	T22968	T22969	det	The,numbers
R6698	T22969	T22970	nsubj	numbers,indicates
R6699	T22971	T22969	prep	on,numbers
R6700	T22972	T22973	det	the,bars
R6701	T22973	T22971	pobj	bars,on
R6702	T22974	T22975	det	the,number
R6703	T22975	T22970	dobj	number,indicates
R6704	T22976	T22975	prep	of,number
R6705	T22977	T22976	pobj	mice,of
R6706	T22978	T22977	acl	analyzed,mice
R6707	T22979	T22970	punct	.,indicates
R6708	T22981	T22982	punct	,*
R6709	T22983	T22981	punct	", ",*
R6710	T22984	T22985	advmod	Significantly,different
R6711	T22985	T22981	amod	different,*
R6712	T22986	T22985	prep	from,different
R6713	T22987	T22988	punct	+,+
R6714	T22988	T22986	punct	+,from
R6715	T22989	T22988	punct	/,+
R6716	T22990	T22991	punct	(,0.001
R6717	T22991	T22985	parataxis	0.001,different
R6718	T22992	T22991	nsubj	P,0.001
R6719	T22993	T22991	punct	<,0.001
R6720	T22994	T22991	punct	),0.001
R6721	T22995	T22982	punct	;,**
R6722	T22996	T22982	punct	", ",**
R6723	T22997	T22998	advmod	significantly,different
R6724	T22998	T22982	amod	different,**
R6725	T22999	T22998	prep	from,different
R6726	T23000	T23001	punct	+,+
R6727	T23001	T22999	punct	+,from
R6728	T23002	T23001	punct	/,+
R6729	T23003	T23001	cc	and,+
R6730	T23004	T23005	punct	+,-
R6731	T23005	T23001	conj	-,+
R6732	T23006	T23005	punct	/,-
R6733	T23007	T23008	punct	(,0.001
R6734	T23008	T22998	parataxis	0.001,different
R6735	T23009	T23008	nsubj	P,0.001
R6736	T23010	T23008	punct	<,0.001
R6737	T23011	T23008	punct	),0.001
R6738	T23012	T22982	punct	.,**
R6739	T23655	T23656	amod	Transgenic,production
R6740	T23657	T23656	compound	mouse,production
R6741	T23658	T23656	cc	and,production
R6742	T23659	T23656	conj	characterization,production
R6743	T23660	T23656	punct	.,production
R6744	T23662	T23663	meta	A,strategy
R6745	T23664	T23663	punct	", ",strategy
R6746	T23665	T23663	amod	Transgenic,strategy
R6747	T23666	T23663	acl	used,strategy
R6748	T23667	T23668	aux	to,produce
R6749	T23668	T23666	advcl	produce,used
R6750	T23669	T23668	dobj	mice,produce
R6751	T23670	T23671	dep	that,express
R6752	T23671	T23669	relcl	express,mice
R6753	T23672	T23673	amod	human,E2
R6754	T23673	T23671	dobj	E2,express
R6755	T23674	T23663	punct	.,strategy
R6756	T23676	T23677	nmod	LAP,tTA
R6757	T23677	T23679	nmod	tTA,mice
R6758	T23678	T23677	punct	-,tTA
R6759	T23679	T23681	nsubjpass	mice,described
R6760	T23680	T23679	amod	transgenic,mice
R6761	T23682	T23681	aux	have,described
R6762	T23683	T23681	auxpass	been,described
R6763	T23684	T23681	advmod	previously,described
R6764	T23685	T23686	punct	[,34
R6765	T23686	T23681	parataxis	34,described
R6766	T23687	T23686	punct	],34
R6767	T23688	T23681	punct	.,described
R6768	T23690	T23691	det	These,mice
R6769	T23691	T23692	nsubj	mice,express
R6770	T23693	T23694	det	the,transactivator
R6771	T23694	T23692	dobj	transactivator,express
R6772	T23695	T23696	npadvmod	tetracycline,controlled
R6773	T23696	T23694	amod	controlled,transactivator
R6774	T23697	T23696	punct	-,controlled
R6775	T23698	T23694	punct	(,transactivator
R6776	T23699	T23694	appos	tTA,transactivator
R6777	T23700	T23694	punct	),transactivator
R6778	T23701	T23694	prep	from,transactivator
R6779	T23702	T23703	det	the,promoter
R6780	T23703	T23701	pobj	promoter,from
R6781	T23704	T23705	npadvmod	liver,specific
R6782	T23705	T23703	amod	specific,promoter
R6783	T23706	T23703	compound	LAP,promoter
R6784	T23707	T23692	punct	.,express
R6785	T23709	T23710	det	The,transgene
R6786	T23710	T23714	nsubj	transgene,contains
R6787	T23711	T23712	compound	TRE,E2
R6788	T23712	T23710	compound	E2,transgene
R6789	T23713	T23712	punct	-,E2
R6790	T23715	T23716	det	the,element
R6791	T23716	T23714	dobj	element,contains
R6792	T23717	T23716	compound	tetracycline,element
R6793	T23718	T23716	compound	response,element
R6794	T23719	T23716	punct	(,element
R6795	T23720	T23716	appos	TRE,element
R6796	T23721	T23716	punct	),element
R6797	T23722	T23716	prep	as,element
R6798	T23723	T23722	pobj	part,as
R6799	T23724	T23723	prep	of,part
R6800	T23725	T23726	det	the,promoter
R6801	T23726	T23724	pobj	promoter,of
R6802	T23727	T23716	punct	", ",element
R6803	T23728	T23729	det	a,intron
R6804	T23729	T23716	conj	intron,element
R6805	T23730	T23729	amod	synthetic,intron
R6806	T23731	T23732	punct	(,line
R6807	T23732	T23729	parataxis	line,intron
R6808	T23733	T23732	amod	thin,line
R6809	T23734	T23732	punct	),line
R6810	T23735	T23729	punct	", ",intron
R6811	T23736	T23737	det	the,cDNA
R6812	T23737	T23729	conj	cDNA,intron
R6813	T23738	T23737	amod	human,cDNA
R6814	T23739	T23737	compound	E2,cDNA
R6815	T23740	T23737	punct	", ",cDNA
R6816	T23741	T23742	det	an,spacer
R6817	T23742	T23737	conj	spacer,cDNA
R6818	T23743	T23742	compound	alanine,spacer
R6819	T23744	T23742	punct	", ",spacer
R6820	T23745	T23746	det	a,tag
R6821	T23746	T23742	conj	tag,spacer
R6822	T23747	T23748	compound	c,myc
R6823	T23748	T23746	compound	myc,tag
R6824	T23749	T23748	punct	-,myc
R6825	T23750	T23746	compound	epitope,tag
R6826	T23751	T23746	punct	", ",tag
R6827	T23752	T23746	cc	and,tag
R6828	T23753	T23754	npadvmod	SV40,derived
R6829	T23754	T23755	amod	derived,sequence
R6830	T23755	T23746	conj	sequence,tag
R6831	T23756	T23755	compound	polyadenylation,sequence
R6832	T23757	T23714	punct	.,contains
R6833	T23759	T23760	det	This,construct
R6834	T23760	T23761	nsubjpass	construct,used
R6835	T23762	T23761	auxpass	was,used
R6836	T23763	T23764	aux	to,create
R6837	T23764	T23761	advcl	create,used
R6838	T23765	T23766	amod	several,lines
R6839	T23766	T23764	dobj	lines,create
R6840	T23767	T23766	prep	of,lines
R6841	T23768	T23769	amod	transgenic,mice
R6842	T23769	T23767	pobj	mice,of
R6843	T23770	T23761	punct	.,used
R6844	T23772	T23773	meta	B,analysis
R6845	T23774	T23773	punct	", ",analysis
R6846	T23775	T23776	compound	Western,blot
R6847	T23776	T23773	compound	blot,analysis
R6848	T23777	T23773	prep	of,analysis
R6849	T23778	T23779	compound	E2,protein
R6850	T23779	T23777	pobj	protein,of
R6851	T23780	T23779	prep	in,protein
R6852	T23781	T23780	pobj	liver,in
R6853	T23782	T23781	prep	of,liver
R6854	T23783	T23784	nmod	control,mice
R6855	T23784	T23782	pobj	mice,of
R6856	T23785	T23783	cc	and,control
R6857	T23786	T23783	conj	intermediate,control
R6858	T23787	T23784	compound	MSUD,mice
R6859	T23788	T23773	punct	.,analysis
R6860	T23791	T23792	mark	that,was
R6861	T23792	T23790	ccomp	was,Note
R6862	T23793	T23794	det	the,amount
R6863	T23794	T23792	nsubj	amount,was
R6864	T23795	T23794	prep	of,amount
R6865	T23796	T23797	amod	human,protein
R6866	T23797	T23795	pobj	protein,of
R6867	T23798	T23797	compound	E2,protein
R6868	T23799	T23800	punct	(,MW
R6869	T23800	T23797	parataxis	MW,protein
R6870	T23801	T23800	amod	predicted,MW
R6871	T23802	T23803	punct	~,54
R6872	T23803	T23804	nummod	54,Kd
R6873	T23804	T23800	appos	Kd,MW
R6874	T23805	T23800	punct	),MW
R6875	T23806	T23794	prep	in,amount
R6876	T23807	T23806	pobj	mice,in
R6877	T23808	T23807	prep	from,mice
R6878	T23809	T23810	compound	Lines,A
R6879	T23810	T23808	pobj	A,from
R6880	T23811	T23810	cc	and,A
R6881	T23812	T23813	nummod	525,A
R6882	T23813	T23810	conj	A,A
R6883	T23814	T23792	acomp	variable,was
R6884	T23815	T23792	cc	but,was
R6885	T23816	T23817	prep	in,was
R6886	T23817	T23792	conj	was,was
R6887	T23818	T23816	pobj	many,in
R6888	T23819	T23818	prep	of,many
R6889	T23820	T23821	det	the,animals
R6890	T23821	T23819	pobj	animals,of
R6891	T23822	T23823	det	the,amount
R6892	T23823	T23817	nsubj	amount,was
R6893	T23824	T23817	acomp	similar,was
R6894	T23825	T23824	prep	to,similar
R6895	T23826	T23827	det	the,amount
R6896	T23827	T23825	pobj	amount,to
R6897	T23828	T23827	prep	of,amount
R6898	T23829	T23830	compound	mouse,E2
R6899	T23830	T23828	pobj	E2,of
R6900	T23831	T23832	punct	(,Kd
R6901	T23832	T23830	parataxis	Kd,E2
R6902	T23833	T23832	nsubj	MW,Kd
R6903	T23834	T23832	punct	=,Kd
R6904	T23835	T23836	punct	~,47
R6905	T23836	T23832	nummod	47,Kd
R6906	T23837	T23832	punct	),Kd
R6907	T23838	T23827	prep	in,amount
R6908	T23839	T23840	compound	control,animals
R6909	T23840	T23838	pobj	animals,in
R6910	T23841	T23790	punct	.,Note
R6911	T23843	T23844	compound	Re,probing
R6912	T23844	T23846	nsubj	probing,confirmed
R6913	T23845	T23844	punct	-,probing
R6914	T23847	T23844	prep	with,probing
R6915	T23848	T23849	det	a,antibody
R6916	T23849	T23847	pobj	antibody,with
R6917	T23850	T23851	compound	c,myc
R6918	T23851	T23849	compound	myc,antibody
R6919	T23852	T23851	punct	-,myc
R6920	T23853	T23849	compound	tag,antibody
R6921	T23854	T23855	det	the,presence
R6922	T23855	T23846	dobj	presence,confirmed
R6923	T23856	T23855	prep	of,presence
R6924	T23857	T23858	det	the,E2
R6925	T23858	T23856	pobj	E2,of
R6926	T23859	T23860	npadvmod	transgene,derived
R6927	T23860	T23858	amod	derived,E2
R6928	T23861	T23858	punct	", ",E2
R6929	T23862	T23863	compound	c,myc
R6930	T23863	T23865	npadvmod	myc,tagged
R6931	T23864	T23863	punct	-,myc
R6932	T23865	T23858	amod	tagged,E2
R6933	T23866	T23858	punct	", ",E2
R6934	T23867	T23858	amod	human,E2
R6935	T23868	T23846	prep	in,confirmed
R6936	T23869	T23870	amod	transgenic,mice
R6937	T23870	T23868	pobj	mice,in
R6938	T23871	T23868	cc	but,in
R6939	T23872	T23871	neg	not,but
R6940	T23873	T23868	conj	in,in
R6941	T23874	T23873	pobj	controls,in
R6942	T23875	T23846	punct	.,confirmed
R6943	T23877	T23878	compound	Western,blot
R6944	T23878	T23879	compound	blot,analysis
R6945	T23879	T23880	nsubj	analysis,revealed
R6946	T23881	T23879	prep	of,analysis
R6947	T23882	T23881	pobj	brain,of
R6948	T23883	T23884	punct	(,C
R6949	T23884	T23882	parataxis	C,brain
R6950	T23885	T23884	punct	),C
R6951	T23886	T23882	punct	", ",brain
R6952	T23887	T23882	conj	kidney,brain
R6953	T23888	T23889	punct	(,D
R6954	T23889	T23887	parataxis	D,kidney
R6955	T23890	T23889	punct	),D
R6956	T23891	T23887	punct	", ",kidney
R6957	T23892	T23887	cc	and,kidney
R6958	T23893	T23887	conj	muscle,kidney
R6959	T23894	T23895	punct	(,E
R6960	T23895	T23893	parataxis	E,muscle
R6961	T23896	T23895	punct	),E
R6962	T23897	T23898	amod	negligible,amounts
R6963	T23898	T23880	dobj	amounts,revealed
R6964	T23899	T23898	prep	of,amounts
R6965	T23900	T23901	npadvmod	transgene,derived
R6966	T23901	T23902	amod	derived,E2
R6967	T23902	T23899	pobj	E2,of
R6968	T23903	T23880	prep	in,revealed
R6969	T23904	T23905	det	those,tissues
R6970	T23905	T23903	pobj	tissues,in
R6971	T23906	T23880	punct	.,revealed
R6972	T23908	T23909	det	All,blots
R6973	T23909	T23910	nsubjpass	blots,re-probed
R6974	T23911	T23910	auxpass	were,re-probed
R6975	T23912	T23910	prep	with,re-probed
R6976	T23913	T23914	det	an,antibody
R6977	T23914	T23912	pobj	antibody,with
R6978	T23915	T23914	compound	actin,antibody
R6979	T23916	T23917	aux	to,allow
R6980	T23917	T23910	advcl	allow,re-probed
R6981	T23918	T23919	nsubjpass	amount,compared
R6982	T23919	T23917	ccomp	compared,allow
R6983	T23920	T23918	prep	of,amount
R6984	T23921	T23920	pobj	protein,of
R6985	T23922	T23921	acl	loaded,protein
R6986	T23923	T23922	prep	in,loaded
R6987	T23924	T23925	det	each,lane
R6988	T23925	T23923	pobj	lane,in
R6989	T23926	T23919	aux	to,compared
R6990	T23927	T23919	auxpass	be,compared
R6991	T23928	T23910	punct	.,re-probed
R6992	T24446	T24445	prep	of,Characterization
R6993	T24447	T24448	det	the,model
R6994	T24448	T24446	pobj	model,of
R6995	T24449	T24448	amod	intermediate,model
R6996	T24450	T24448	nmod	MSUD,model
R6997	T24451	T24448	amod	murine,model
R6998	T24452	T24445	punct	.,Characterization
R6999	T24454	T24455	meta	A,analysis
R7000	T24456	T24455	punct	", ",analysis
R7001	T24457	T24455	compound	Survival,analysis
R7002	T24458	T24455	prep	of,analysis
R7003	T24459	T24460	amod	transgenic,lines
R7004	T24460	T24458	pobj	lines,of
R7005	T24461	T24460	compound	rescue,lines
R7006	T24462	T24455	punct	.,analysis
R7007	T24464	T24465	dep	Presented,are
R7008	T24466	T24465	nsubj	percentages,are
R7009	T24467	T24466	prep	of,percentages
R7010	T24468	T24467	pobj	mice,of
R7011	T24469	T24468	amod	alive,mice
R7012	T24470	T24469	prep	at,alive
R7013	T24471	T24470	pobj	weaning,at
R7014	T24472	T24468	prep	from,mice
R7015	T24473	T24474	det	each,line
R7016	T24474	T24472	pobj	line,from
R7017	T24475	T24474	amod	transgenic,line
R7018	T24476	T24474	acl	tested,line
R7019	T24477	T24478	dep	that,had
R7020	T24478	T24476	ccomp	had,tested
R7021	T24479	T24480	det	the,genotype
R7022	T24480	T24478	dobj	genotype,had
R7023	T24481	T24480	compound	rescue,genotype
R7024	T24482	T24483	punct	(,homozygous
R7025	T24483	T24478	parataxis	homozygous,had
R7026	T24484	T24483	advmod	i.e.,homozygous
R7027	T24485	T24483	punct	", ",homozygous
R7028	T24486	T24483	prep	for,homozygous
R7029	T24487	T24486	pobj	knockout,for
R7030	T24488	T24487	prep	of,knockout
R7031	T24489	T24490	amod	endogenous,E2
R7032	T24490	T24488	pobj	E2,of
R7033	T24491	T24483	cc	and,homozygous
R7034	T24492	T24483	conj	positive,homozygous
R7035	T24493	T24492	prep	for,positive
R7036	T24494	T24495	preconj	both,transgenes
R7037	T24495	T24493	pobj	transgenes,for
R7038	T24496	T24495	det	the,transgenes
R7039	T24497	T24498	nmod	LAP,tTA
R7040	T24498	T24495	nmod	tTA,transgenes
R7041	T24499	T24498	punct	-,tTA
R7042	T24500	T24498	cc	and,tTA
R7043	T24501	T24502	compound	TRE,E2
R7044	T24502	T24498	conj	E2,tTA
R7045	T24503	T24502	punct	-,E2
R7046	T24504	T24483	punct	),homozygous
R7047	T24505	T24465	punct	.,are
R7048	T24507	T24508	advmod	Also,is
R7049	T24509	T24508	dep	plotted,is
R7050	T24510	T24511	det	the,frequency
R7051	T24511	T24508	nsubj	frequency,is
R7052	T24512	T24511	amod	theoretical,frequency
R7053	T24513	T24511	amod	maximum,frequency
R7054	T24514	T24515	prep	at,expected
R7055	T24515	T24511	relcl	expected,frequency
R7056	T24516	T24514	pobj	which,at
R7057	T24517	T24518	det	this,genotype
R7058	T24518	T24515	nsubjpass	genotype,expected
R7059	T24519	T24515	auxpass	is,expected
R7060	T24520	T24515	prep	in,expected
R7061	T24521	T24522	det	this,population
R7062	T24522	T24520	pobj	population,in
R7063	T24523	T24522	prep	of,population
R7064	T24524	T24523	pobj	animals,of
R7065	T24525	T24508	punct	.,is
R7066	T24527	T24528	det	The,numbers
R7067	T24528	T24529	nsubj	numbers,indicates
R7068	T24530	T24528	prep	on,numbers
R7069	T24531	T24532	det	the,bars
R7070	T24532	T24530	pobj	bars,on
R7071	T24533	T24534	det	the,numbers
R7072	T24534	T24529	dobj	numbers,indicates
R7073	T24535	T24534	prep	of,numbers
R7074	T24536	T24535	pobj	observations,of
R7075	T24537	T24534	prep	for,numbers
R7076	T24538	T24539	det	each,line
R7077	T24539	T24537	pobj	line,for
R7078	T24540	T24529	punct	.,indicates
R7079	T24542	T24543	meta	B,Ratio
R7080	T24544	T24543	punct	", ",Ratio
R7081	T24545	T24543	prep	of,Ratio
R7082	T24546	T24547	amod	total,BCAA
R7083	T24547	T24545	pobj	BCAA,of
R7084	T24548	T24543	prep	to,Ratio
R7085	T24549	T24548	pobj	alanine,to
R7086	T24550	T24543	prep	in,Ratio
R7087	T24551	T24550	pobj	blood,in
R7088	T24552	T24551	prep	of,blood
R7089	T24553	T24552	pobj	mice,of
R7090	T24554	T24543	prep	from,Ratio
R7091	T24555	T24554	pobj	controls,from
R7092	T24556	T24555	cc	and,controls
R7093	T24557	T24558	compound	Lines,A
R7094	T24558	T24555	conj	A,controls
R7095	T24559	T24558	cc	and,A
R7096	T24560	T24558	conj	525A,A
R7097	T24561	T24543	punct	.,Ratio
R7098	T24563	T24564	amod	Total,BCAA
R7099	T24564	T24565	nsubj	BCAA,represent
R7100	T24566	T24567	det	the,sum
R7101	T24567	T24565	dobj	sum,represent
R7102	T24568	T24567	prep	of,sum
R7103	T24569	T24568	pobj	leucine,of
R7104	T24570	T24569	punct	", ",leucine
R7105	T24571	T24569	conj	isoleucine,leucine
R7106	T24572	T24571	punct	", ",isoleucine
R7107	T24573	T24571	cc	and,isoleucine
R7108	T24574	T24571	conj	valine,isoleucine
R7109	T24575	T24565	punct	.,represent
R7110	T24577	T24578	compound	BCAA,alanine
R7111	T24578	T24580	compound	alanine,values
R7112	T24579	T24578	punct	/,alanine
R7113	T24580	T24581	nsubj	values,were
R7114	T24582	T24583	advmod	significantly,greater
R7115	T24583	T24581	acomp	greater,were
R7116	T24584	T24583	prep	for,greater
R7117	T24585	T24586	compound	Lines,A
R7118	T24586	T24584	pobj	A,for
R7119	T24587	T24586	cc	and,A
R7120	T24588	T24586	conj	525A,A
R7121	T24589	T24583	prep	compared,greater
R7122	T24590	T24589	prep	to,compared
R7123	T24591	T24590	pobj	controls,to
R7124	T24592	T24581	prep	at,were
R7125	T24593	T24594	det	all,ages
R7126	T24594	T24592	pobj	ages,at
R7127	T24595	T24594	acl	tested,ages
R7128	T24596	T24581	punct	.,were
R7129	T24598	T24599	det	The,numbers
R7130	T24599	T24600	nsubj	numbers,indicates
R7131	T24601	T24599	prep	on,numbers
R7132	T24602	T24603	det	the,bars
R7133	T24603	T24601	pobj	bars,on
R7134	T24604	T24605	det	the,numbers
R7135	T24605	T24600	dobj	numbers,indicates
R7136	T24606	T24605	prep	of,numbers
R7137	T24607	T24606	pobj	samples,of
R7138	T24608	T24607	acl	analyzed,samples
R7139	T24609	T24600	punct	.,indicates
R7140	T24611	T24612	punct	*,0.01
R7141	T24612	T24616	ccomp	0.01,0.005
R7142	T24613	T24612	punct	", ",0.01
R7143	T24614	T24612	nsubj	P,0.01
R7144	T24615	T24612	punct	≤,0.01
R7145	T24617	T24616	punct	;,0.005
R7146	T24618	T24616	punct	**,0.005
R7147	T24619	T24616	punct	", ",0.005
R7148	T24620	T24616	nsubj	P,0.005
R7149	T24621	T24616	punct	<,0.005
R7150	T24622	T24616	punct	.,0.005
R7151	T24624	T24625	meta	C,activity
R7152	T24626	T24625	punct	", ",activity
R7153	T24627	T24625	compound	BCKDH,activity
R7154	T24628	T24625	compound	enzyme,activity
R7155	T24629	T24625	prep	in,activity
R7156	T24630	T24629	pobj	liver,in
R7157	T24631	T24630	prep	of,liver
R7158	T24632	T24633	nmod	control,mice
R7159	T24633	T24631	pobj	mice,of
R7160	T24634	T24632	cc	and,control
R7161	T24635	T24636	compound	Lines,A
R7162	T24636	T24632	conj	A,control
R7163	T24637	T24636	cc	and,A
R7164	T24638	T24636	conj	525A,A
R7165	T24639	T24625	punct	.,activity
R7166	T24641	T24642	punct	*,0.001
R7167	T24642	T24646	ccomp	0.001,0.0001
R7168	T24643	T24642	punct	", ",0.001
R7169	T24644	T24642	nsubj	P,0.001
R7170	T24645	T24642	punct	≤,0.001
R7171	T24647	T24646	punct	;,0.0001
R7172	T24648	T24646	punct	**,0.0001
R7173	T24649	T24646	punct	", ",0.0001
R7174	T24650	T24646	nsubj	P,0.0001
R7175	T24651	T24646	punct	≤,0.0001
R7176	T24652	T24646	punct	.,0.0001
R7177	T24654	T24655	meta	D,curves
R7178	T24656	T24655	punct	", ",curves
R7179	T24657	T24655	compound	Survival,curves
R7180	T24658	T24655	prep	for,curves
R7181	T24659	T24658	pobj	mice,for
R7182	T24660	T24659	prep	from,mice
R7183	T24661	T24662	compound	Lines,A
R7184	T24662	T24660	pobj	A,from
R7185	T24663	T24662	cc	and,A
R7186	T24664	T24662	conj	525A,A
R7187	T24665	T24655	punct	.,curves
R7188	T24667	T24668	compound	Rescue,mice
R7189	T24668	T24669	nsubjpass	mice,monitored
R7190	T24670	T24668	amod	alive,mice
R7191	T24671	T24670	prep	at,alive
R7192	T24672	T24671	pobj	weaning,at
R7193	T24673	T24669	auxpass	were,monitored
R7194	T24674	T24675	mark	until,were
R7195	T24675	T24669	advcl	were,monitored
R7196	T24676	T24675	nsubj	they,were
R7197	T24677	T24675	acomp	moribund,were
R7198	T24678	T24677	cc	and,moribund
R7199	T24679	T24680	advmod	subsequently,sacrificed
R7200	T24680	T24677	conj	sacrificed,moribund
R7201	T24681	T24675	cc	or,were
R7202	T24682	T24683	auxpass	were,found
R7203	T24683	T24675	conj	found,were
R7204	T24684	T24683	advcl	dead,found
R7205	T24685	T24683	prep	in,found
R7206	T24686	T24687	poss	their,cages
R7207	T24687	T24685	pobj	cages,in
R7208	T24688	T24669	punct	.,monitored
R7209	T24775	T24774	prep	of,Summary
R7210	T24776	T24777	amod	additional,levels
R7211	T24777	T24775	pobj	levels,of
R7212	T24778	T24777	compound	blood,levels
R7213	T24779	T24780	compound	amino,acid
R7214	T24780	T24777	compound	acid,levels
R7215	T24781	T24777	prep	in,levels
R7216	T24782	T24783	det	the,model
R7217	T24783	T24781	pobj	model,in
R7218	T24784	T24783	amod	classic,model
R7219	T24785	T24783	compound	MSUD,model
R7220	T24786	T24783	cc	and,model
R7221	T24787	T24788	compound	control,littermates
R7222	T24788	T24783	conj	littermates,model
R7223	T24789	T24790	mark	as,determined
R7224	T24790	T24777	advcl	determined,levels
R7225	T24791	T24790	prep	by,determined
R7226	T24792	T24793	amod	tandem,spectrometry
R7227	T24793	T24791	pobj	spectrometry,by
R7228	T24794	T24793	compound	mass,spectrometry
R7229	T24795	T24774	punct	.,Summary
R7230	T24797	T24798	det	All,samples
R7231	T24798	T24799	nsubjpass	samples,collected
R7232	T24800	T24799	auxpass	were,collected
R7233	T24801	T24799	prep	on,collected
R7234	T24802	T24803	det	the,day
R7235	T24803	T24801	pobj	day,on
R7236	T24804	T24803	prep	of,day
R7237	T24805	T24804	pobj	birth,of
R7238	T24806	T24799	punct	.,collected
R7239	T24808	T24809	det	All,values
R7240	T24809	T24810	nsubj	values,are
R7241	T24811	T24810	attr	mean,are
R7242	T24812	T24811	cc	+,mean
R7243	T24813	T24812	punct	/,+
R7244	T24814	T24812	punct	-,+
R7245	T24815	T24811	conj	SEM,mean
R7246	T24816	T24810	punct	.,are
R7247	T24915	T24914	prep	of,Summary
R7248	T24916	T24917	amod	additional,levels
R7249	T24917	T24915	pobj	levels,of
R7250	T24918	T24917	compound	blood,levels
R7251	T24919	T24920	compound	amino,acid
R7252	T24920	T24917	compound	acid,levels
R7253	T24921	T24917	prep	in,levels
R7254	T24922	T24923	det	the,model
R7255	T24923	T24921	pobj	model,in
R7256	T24924	T24923	amod	intermediate,model
R7257	T24925	T24923	compound	MSUD,model
R7258	T24926	T24923	cc	and,model
R7259	T24927	T24928	compound	littermate,controls
R7260	T24928	T24923	conj	controls,model
R7261	T24929	T24930	mark	as,determined
R7262	T24930	T24917	advcl	determined,levels
R7263	T24931	T24930	prep	by,determined
R7264	T24932	T24933	amod	tandem,spectrometry
R7265	T24933	T24931	pobj	spectrometry,by
R7266	T24934	T24933	compound	mass,spectrometry
R7267	T24935	T24914	punct	.,Summary
R7268	T24937	T24938	nsubjpass	Samples,collected
R7269	T24939	T24938	auxpass	were,collected
R7270	T24940	T24938	prep	from,collected
R7271	T24941	T24940	pobj	mice,from
R7272	T24942	T24943	dep	that,were
R7273	T24943	T24941	relcl	were,mice
R7274	T24944	T24945	quantmod	4,6
R7275	T24945	T24947	nummod	6,weeks
R7276	T24946	T24945	punct	–,6
R7277	T24947	T24943	attr	weeks,were
R7278	T24948	T24947	prep	of,weeks
R7279	T24949	T24948	pobj	age,of
R7280	T24950	T24938	punct	.,collected
R7281	T24952	T24953	det	All,values
R7282	T24953	T24954	nsubj	values,are
R7283	T24955	T24954	attr	mean,are
R7284	T24956	T24955	cc	+,mean
R7285	T24957	T24956	punct	/,+
R7286	T24958	T24956	punct	-,+
R7287	T24959	T24955	conj	SEM,mean
R7288	T24960	T24954	punct	.,are
R3345	T12266	T12268	punct	+,mice
R3347	T12268	T12264	pobj	mice,in
R3348	T12269	T12270	advmod	readily,detectable
R3349	T12270	T12256	acomp	detectable,was
R3350	T12271	T12256	punct	.,was
R3351	T12273	T12274	prep	In,was
R3352	T12275	T12276	amod	marked,contrast
R3353	T12276	T12273	pobj	contrast,In
R3354	T12277	T12274	punct	", ",was
R3355	T12278	T12279	compound	BCKDH,activity
R3356	T12279	T12274	nsubj	activity,was
R3357	T12280	T12281	advmod	completely,absent
R3358	T12281	T12274	acomp	absent,was
R3359	T12282	T12274	prep	in,was
R3360	T12283	T12284	punct	-,-
R3361	T12284	T12286	punct	-,livers
R3362	T12285	T12284	punct	/,-
R3410	T12339	T12340	nsubjpass	Immunohistochemistry,used
R3411	T12341	T12339	prep	with,Immunohistochemistry
R3412	T12342	T12343	det	an,antibody
R3413	T12343	T12341	pobj	antibody,with
R3414	T12344	T12345	npadvmod	E2,specific
R3415	T12345	T12343	amod	specific,antibody
R3416	T12346	T12340	auxpass	was,used
R3417	T12347	T12348	aux	to,examine
R3418	T12348	T12340	advcl	examine,used
R3419	T12349	T12350	compound	E2,protein
R3721	T12671	T12667	pobj	ratio,as
R3722	T12672	T12659	punct	.,expressed
R3723	T12674	T12675	mark	As,shown
R3724	T12675	T12676	advcl	shown,was
R3725	T12677	T12675	prep	in,shown
R3726	T12678	T12679	compound	Figure,2C
R3727	T12679	T12677	pobj	2C,in
R3728	T12680	T12676	punct	", ",was
R3729	T12681	T12682	det	this,ratio
R3730	T12682	T12676	nsubj	ratio,was
R3731	T12683	T12682	prep	in,ratio
R3732	T12684	T12685	punct	-,-
R3733	T12685	T12687	punct	-,pups
R3734	T12686	T12685	punct	/,-
R3735	T12687	T12683	pobj	pups,in
R3736	T12688	T12689	advmod	more,6
R3737	T12689	T12691	quantmod	6,fold
R3738	T12690	T12689	quantmod	than,6
R3739	T12691	T12693	advmod	fold,higher
R3740	T12692	T12691	punct	-,fold
R3741	T12693	T12676	acomp	higher,was
R3742	T12694	T12693	prep	than,higher
R3743	T12695	T12696	punct	+,+
R3744	T12696	T12698	punct	+,littermates
R3745	T12697	T12696	punct	/,+
R3746	T12698	T12694	pobj	littermates,than
R3747	T12699	T12696	cc	or,+
R3774	T12729	T12730	prep	In,lack
R3775	T12731	T12729	pobj	summary,In
R3776	T12732	T12730	punct	", ",lack
R3777	T12733	T12734	compound	E2,mice
R3778	T12734	T12730	nsubj	mice,lack
R3779	T12735	T12734	compound	knockout,mice
R3780	T12736	T12737	nmod	BCKDH,activity
R3781	T12737	T12730	dobj	activity,lack
R3782	T12738	T12737	amod	enzymatic,activity
R3783	T12739	T12737	punct	", ",activity
R3784	T12740	T12741	compound	E2,immunoreactivity
R3785	T12741	T12737	appos	immunoreactivity,activity
R3786	T12742	T12730	punct	", ",lack
R3787	T12743	T12730	cc	and,lack
R3788	T12744	T12730	conj	have,lack
R3789	T12745	T12746	advmod	markedly,elevated
R3790	T12746	T12747	amod	elevated,levels
R3791	T12747	T12744	dobj	levels,have
R3792	T12748	T12747	prep	of,levels
R3793	T12749	T12748	pobj	BCAA,of
R3794	T12750	T12744	prep	in,have
R3795	T12751	T12752	det	the,blood
R3796	T12752	T12750	pobj	blood,in
R3797	T12753	T12752	cc	and,blood
R3798	T12754	T12752	conj	urine,blood
R3799	T12755	T12730	punct	.,lack
R3800	T12757	T12758	det	These,derangements
R3801	T12758	T12760	nsubj	derangements,result
R3802	T12759	T12758	amod	metabolic,derangements
R643	T3628	T3629	det	The,component
R987	T3995	T3970	punct	.,are
R988	T3997	T3998	prep	Because,is
R993	T4001	T3997	pobj	options,Because
R3928	T15827	T15828	det	The,transgene
R3929	T15828	T15832	nsubj	transgene,directs
R3930	T15829	T15830	compound	LAP,tTA
R3931	T15830	T15828	compound	tTA,transgene
R3932	T15831	T15830	punct	-,tTA
R3933	T15833	T15834	punct	[,34
R3934	T15834	T15828	parataxis	34,transgene
R3935	T15835	T15834	punct	],34
R3936	T15836	T15837	amod	high,levels
R3937	T15837	T15832	dobj	levels,directs
R3938	T15838	T15837	prep	of,levels
R3939	T15839	T15840	npadvmod	liver,specific
R3940	T15840	T15841	amod	specific,expression
R3941	T15841	T15838	pobj	expression,of
R3942	T15842	T15841	prep	of,expression
R3943	T15843	T15844	det	the,transactivator
R3993	T15897	T15898	nmod	LAP,tTA
R3994	T15898	T15900	nmod	tTA,mice
R3995	T15899	T15898	punct	-,tTA
R3996	T15903	T15902	auxpass	w,e
R3997	T15904	T15902	advcl	re,e
R3998	T15919	T15920	amod	c,e
R3999	T15923	T15922	cc	and,d
R4000	T15924	T15922	conj	c,d
R4001	T15930	T15929	acl	a,r
R4002	T15932	T15928	aux	t,r
R4003	T15933	T15928	auxpass	e,r
R4004	T15937	T15936	agent	by,zed
R4005	T15938	T15939	det	the,laboratory
R4006	T15939	T15937	pobj	laboratory,by
R4007	T15940	T15939	compound	Bujard,laboratory
R4291	T16290	T16289	pcomp	rescuing,at
R4292	T16291	T16292	det	the,phenotype
R4294	T16292	T16290	dobj	phenotype,rescuing
R4295	T16293	T16292	amod	neonatal,phenotype
R4296	T16294	T16292	amod	lethal,phenotype
R4298	T16295	T16292	prep	of,phenotype
R4299	T16296	T16297	det	the,knockout
R4300	T16297	T16295	pobj	knockout,of
R4301	T16298	T16297	compound	E2,knockout
R4303	T16299	T16280	punct	.,appears
R4304	T16301	T16302	prep	In,failed
R4306	T16303	T16301	pobj	contrast,In
R4307	T16304	T16302	punct	", ",failed
R4308	T16305	T16306	compound	line,520B
R4310	T16306	T16302	nsubj	520B,failed
R4312	T16307	T16302	advmod	completely,failed
R4313	T16308	T16309	aux	to,rescue
R4314	T16309	T16302	xcomp	rescue,failed
R4315	T16310	T16311	det	the,phenotype
R4317	T16311	T16309	dobj	phenotype,rescue
R4319	T16312	T16311	amod	neonatal,phenotype
R4320	T16313	T16311	amod	lethal,phenotype
R4321	T16314	T16302	punct	.,failed
R4323	T16316	T16317	det	All,lines
R4324	T16317	T16319	nsubj	lines,produced
R4325	T16318	T16317	amod	other,lines
R4327	T16320	T16317	acl	tested,lines
R4329	T16321	T16322	amod	surviving,animals
R4330	T16322	T16319	dobj	animals,produced
R4331	T16323	T16322	compound	rescue,animals
R4333	T16324	T16319	prep	at,produced
R4334	T16325	T16326	det	a,frequency
R4335	T16326	T16324	pobj	frequency,at
R4337	T16327	T16326	prep	between,frequency
R4338	T16328	T16329	nummod	1,%
R4339	T16329	T16327	pobj	%,between
R4341	T16330	T16328	cc	and,1
R4342	T16331	T16328	conj	5,1
R4343	T16332	T16329	prep	of,%
R4353	T16341	T16340	nsubj	n,i
R4360	T16352	T16353	advmod	s,e
R4361	T16353	T16351	acomp	e,were
R4372	T16363	T16362	cc	d,or
R4369	T16380	T16381	compound	Fig.,4B
R4370	T16381	T16382	nsubj	4B,shows
R4371	T16383	T16384	det	the,results
R4373	T16384	T16382	dobj	results,shows
R4374	T16385	T16384	prep	of,results
R4375	T16367	T16366	pobj	ai,t
R4376	T16386	T16387	compound	blood,analysis
R4377	T16371	T16370	conj	c,d
R4378	T16387	T16385	pobj	analysis,of
R4379	T16372	T16373	poss	h,a
R4380	T16388	T16389	compound	amino,acid
R4381	T16389	T16387	compound	acid,analysis
R4382	T16376	T16377	amod	a,cterization
R4383	T16390	T16384	acl	presented,results
R4384	T16391	T16390	prep	as,presented
R4385	T16392	T16393	det	a,ratio
R4386	T16393	T16391	pobj	ratio,as
R4387	T16394	T16393	prep	of,ratio
R4389	T16395	T16396	amod	total,BCAA
R4392	T16396	T16394	pobj	BCAA,of
R4396	T16397	T16393	prep	to,ratio
R4400	T16398	T16397	pobj	alanine,to
R4533	T16440	T16439	pobj	controls,between
R4537	T16441	T16440	cc	and,controls
R4540	T16442	T16440	conj	knockouts,controls
R4544	T16443	T16444	punct	(,see
R4548	T16444	T16428	parataxis	see,are
R4551	T16445	T16446	compound	Figure,2C
R4552	T16446	T16444	dobj	2C,see
R4553	T16447	T16444	punct	),see
R4556	T16448	T16426	punct	.,Note
R4563	T16450	T16451	compound	Blood,levels
R4565	T16451	T16452	nsubjpass	levels,reduced
R4568	T16453	T16451	prep	of,levels
R4574	T16454	T16453	pobj	alanine,of
R4577	T16455	T16454	punct	", ",alanine
R4580	T16456	T16454	conj	glutamate,alanine
R4583	T16457	T16456	punct	", ",glutamate
R4586	T16458	T16456	cc	and,glutamate
R4590	T16459	T16456	conj	glutamine,glutamate
R4593	T16460	T16452	auxpass	were,reduced
R4597	T16461	T16452	prep	in,reduced
R4601	T16462	T16463	compound	Line,A
R4605	T16463	T16464	compound	A,mice
R4609	T16464	T16461	pobj	mice,in
R4616	T16465	T16452	punct	", ",reduced
R4620	T16466	T16467	mark	as,was
R4623	T16467	T16452	advcl	was,reduced
R4626	T16468	T16467	nsubj	glutamate,was
R4629	T16469	T16468	prep	in,glutamate
R4633	T16470	T16471	compound	Line,525A
R4636	T16471	T16472	compound	525A,mice
R4640	T16472	T16469	pobj	mice,in
R4644	T16473	T16468	punct	", ",glutamate
R4648	T16474	T16468	prep	compared,glutamate
R4652	T16475	T16474	prep	to,compared
R4656	T16476	T16475	pobj	controls,to
R4658	T16477	T16478	punct	(,Table
R4661	T16478	T16467	parataxis	Table,was
R4667	T16479	T16478	nummod	2,Table
R4671	T16480	T16478	punct	),Table
R4672	T16481	T16452	punct	.,reduced
R4388	T16484	T16485	mark	Because,demonstrated
R4390	T16485	T16503	advcl	demonstrated,examined
R4391	T16486	T16487	det	the,mice
R4393	T16487	T16485	nsubjpass	mice,demonstrated
R4394	T16488	T16489	compound	LAP,tTA
R4395	T16489	T16487	compound	tTA,mice
R4397	T16490	T16489	punct	-,tTA
R4398	T16491	T16492	dep	that,used
R4399	T16492	T16487	relcl	used,mice
R4401	T16493	T16492	auxpass	were,used
R4402	T16494	T16495	aux	to,drive
R4403	T16495	T16492	advcl	drive,used
R4404	T16496	T16495	dobj	expression,drive
R4405	T16497	T16496	prep	of,expression
R4407	T16498	T16499	amod	transgenic,E2
R4408	T16499	T16497	pobj	E2,of
R4409	T16500	T16499	amod	human,E2
R4411	T16501	T16485	aux	have,demonstrated
R4415	T16502	T16485	auxpass	been,demonstrated
R4417	T16504	T16505	aux	to,produce
R4418	T16505	T16485	xcomp	produce,demonstrated
R4419	T16506	T16507	npadvmod	liver,specific
R4421	T16507	T16508	amod	specific,expression
R4422	T16508	T16505	dobj	expression,produce
R4423	T16509	T16510	punct	[,34
R4425	T16510	T16485	parataxis	34,demonstrated
R4426	T16511	T16510	punct	],34
R4427	T16512	T16503	punct	", ",examined
R4429	T16513	T16514	compound	BCKDH,activity
R4430	T16514	T16503	nsubjpass	activity,examined
R4431	T16515	T16514	compound	enzyme,activity
R4433	T16516	T16514	cc	and,activity
R4434	T16517	T16514	conj	production,activity
R4435	T16518	T16517	prep	of,production
R4437	T16519	T16520	amod	human,protein
R4438	T16520	T16518	pobj	protein,of
R6054	T21108	T21109	punct	[,46
R6063	T21109	T21097	parataxis	46,Because
R6068	T21110	T21109	nummod	35,46
R6071	T21111	T21109	punct	",",46
R6074	T21112	T21109	nummod	36,46
R6078	T21113	T21109	punct	",",46
R6081	T21114	T21109	nummod	45,46
R6085	T21115	T21109	punct	",",46
R6088	T21116	T21109	punct	],46

craft-ca-core-ex-dev

Below, discontinuous spans are shown in the chain model. You can change it to the bag model.

Id	Subject	Object	Predicate	Lexical cue
T24441	26163-26167	NCBITaxon:10088	denotes	mice
T24444	26277-26287	GO_EXT:killing	denotes	sacrificed
T24443	26198-26202	NCBITaxon:10088	denotes	mice
T24442	26191-26197	SO_EXT:sequence_rescue_process	denotes	Rescue
T24913	27073-27077	NCBITaxon:10088	denotes	mice
T24912	26929-26939	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T24911	26923-26928	UBERON:0000178	denotes	blood
T24440	26104-26108	NCBITaxon:10088	denotes	mice
T24439	26066-26071	UBERON:0002107	denotes	liver
T24438	26047-26053	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T24437	25839-25846	CHEBI_SO_EXT:alanine	denotes	alanine
T24436	25834-25838	CHEBI:22918	denotes	BCAA
T24435	25826-25832	CHEBI_SO_EXT:valine	denotes	valine
T24434	25810-25820	CHEBI_SO_EXT:isoleucine	denotes	isoleucine
T24433	25801-25808	CHEBI_SO_EXT:leucine	denotes	leucine
T24432	25775-25779	CHEBI:22918	denotes	BCAA
T24431	25728-25732	NCBITaxon:10088	denotes	mice
T24430	25719-25724	UBERON:0000178	denotes	blood
T24429	25708-25715	CHEBI_SO_EXT:alanine	denotes	alanine
T24428	25700-25704	CHEBI:22918	denotes	BCAA
T24427	25596-25603	NCBITaxon:33208	denotes	animals
T24426	25553-25561	SO_EXT:genotype_or_entity_with_genotype	denotes	genotype
T24425	25476-25486	SO_EXT:0000902	denotes	transgenes
T24424	25473-25475	PR_EXT:000006300	denotes	E2
T24423	25457-25460	PR_EXT:000005308	denotes	LAP
T24422	25428-25430	PR_EXT:000006300	denotes	E2
T24421	25374-25382	SO_EXT:genotype_or_entity_with_genotype	denotes	genotype
T24420	25367-25373	SO_EXT:sequence_rescue_process	denotes	rescue
T24419	25331-25341	SO_EXT:transgenic_entity	denotes	transgenic
T24418	25299-25303	NCBITaxon:10088	denotes	mice
T24417	25256-25262	SO_EXT:sequence_rescue_process	denotes	rescue
T24416	25245-25255	SO_EXT:transgenic_entity	denotes	transgenic
T24415	25207-25213	NCBITaxon:10088	denotes	murine
T23645	22750-22754	NCBITaxon:10088	denotes	mice
T23644	22739-22749	SO_EXT:transgenic_entity	denotes	transgenic
T23643	22733-22735	PR_EXT:000006300	denotes	E2
T23642	22727-22732	NCBITaxon:9606	denotes	human
T23641	22719-22725	CHEBI_SO_EXT:molecular_label_or_mark_or_tag_process	denotes	tagged
T23640	22713-22718	PR_EXT:000000084	denotes	c-myc
T23639	22694-22703	SO_EXT:0000902	denotes	transgene
T23638	22655-22663	GO:0042571	denotes	antibody
T23637	22651-22654	CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag	denotes	tag
T23636	22645-22650	PR_EXT:000000084	denotes	c-myc
T23635	22618-22625	NCBITaxon:33208	denotes	animals
T23634	22592-22594	PR_EXT:000006300	denotes	E2
T23633	22586-22591	NCBITaxon:10088	denotes	mouse
T23632	22538-22545	NCBITaxon:33208	denotes	animals
T23631	22478-22482	NCBITaxon:10088	denotes	mice
T23630	22445-22452	CHEBI_PR_EXT:protein	denotes	protein
T23629	22442-22444	PR_EXT:000006300	denotes	E2
T23628	22436-22441	NCBITaxon:9606	denotes	human
T23627	22406-22410	NCBITaxon:10088	denotes	mice
T23626	22367-22372	UBERON:0002107	denotes	liver
T23625	22356-22363	CHEBI_PR_EXT:protein	denotes	protein
T23624	22353-22355	PR_EXT:000006300	denotes	E2
T23623	22319-22323	NCBITaxon:10088	denotes	mice
T23622	22308-22318	SO_EXT:transgenic_entity	denotes	transgenic
T23621	22262-22271	SO_EXT:engineered_biological_sequence	denotes	construct
T23620	22231-22255	SO_EXT:0000610	denotes	polyadenylation sequence
T23619	22231-22246	GO:0043631	denotes	polyadenylation
T23618	22218-22222	NCBITaxon:10633	denotes	SV40
T23617	22209-22212	CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag	denotes	tag
T23616	22201-22208	CHEBI_SO_EXT:epitope	denotes	epitope
T23615	22195-22200	PR_EXT:000000084	denotes	c-myc
T23614	22177-22184	CHEBI_SO_EXT:alanine	denotes	alanine
T23613	22168-22172	SO_EXT:cDNA	denotes	cDNA
T23612	22165-22167	PR_EXT:000006300	denotes	E2
T23611	22159-22164	NCBITaxon:9606	denotes	human
T23610	22135-22141	SO_EXT:0000188	denotes	intron
T23609	22113-22121	SO_EXT:0000167	denotes	promoter
T23608	22075-22083	GO_EXT:reaction_or_response	denotes	response
T23607	22062-22074	CHEBI:27902	denotes	tetracycline
T23606	22039-22048	SO_EXT:0000902	denotes	transgene
T23605	22036-22038	PR_EXT:000006300	denotes	E2
T23604	22018-22026	SO_EXT:0000167	denotes	promoter
T23603	22014-22017	PR_EXT:000005308	denotes	LAP
T23602	21999-22004	UBERON:0002107	denotes	liver
T23601	21958-21968	GO:0065007	denotes	controlled
T23600	21945-21957	CHEBI:27902	denotes	tetracycline
T23599	21933-21940	GO:0010467	denotes	express
T23598	21928-21932	NCBITaxon:10088	denotes	mice
T23597	21880-21884	NCBITaxon:10088	denotes	mice
T23596	21869-21879	SO_EXT:transgenic_entity	denotes	transgenic
T23595	21861-21864	PR_EXT:000005308	denotes	LAP
T23594	21857-21859	PR_EXT:000006300	denotes	E2
T23593	21851-21856	NCBITaxon:9606	denotes	human
T23592	21843-21850	GO:0010467	denotes	express
T23591	21833-21837	NCBITaxon:10088	denotes	mice
T23590	21797-21807	SO_EXT:transgenic_entity	denotes	Transgenic
T23589	21755-21760	NCBITaxon:10088	denotes	mouse
T23588	21744-21754	SO_EXT:transgenic_entity	denotes	Transgenic
T23654	22976-22983	CHEBI_PR_EXT:protein	denotes	protein
T23653	22948-22956	GO:0042571	denotes	antibody
T23652	22942-22947	PR_EXT:000003676	denotes	actin
T23651	22900-22907	UBERON:0000479	denotes	tissues
T23650	22888-22890	PR_EXT:000006300	denotes	E2
T23649	22870-22879	SO_EXT:0000902	denotes	transgene
T23648	22828-22834	UBERON_EXT:muscle_structure_or_tissue	denotes	muscle
T23647	22812-22818	UBERON:0002113	denotes	kidney
T23646	22801-22806	UBERON:0000955	denotes	brain
T19825	37327-37334	CHEBI_GO_SO_EXT:enzyme	denotes	enzymes
T19824	37272-37285	GO:0005739	denotes	mitochondrial
T19823	37250-37262	GO_EXT:biological_movement_or_translocation_process	denotes	transferable
T19822	37119-37126	CHEBI_GO_EXT:biological_process_or_quality_or_role	denotes	biology
T19821	37008-37017	GO:0032991	denotes	complexes
T19820	37001-37007	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T19819	36935-36941	NCBITaxon:33208	denotes	animal
T19818	36891-36901	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T19817	36885-36890	UBERON:0000178	denotes	blood
T19816	36842-36849	CHEBI:26948	denotes	thiamin
T19815	36797-36802	NCBITaxon:10088	denotes	mouse
T19814	36725-36731	SO_EXT:0001023	denotes	allele
T19813	36714-36724	GO:0010467	denotes	expressing
T19812	36711-36713	PR_EXT:000006300	denotes	E2
T19811	36635-36642	CHEBI:26948	denotes	thiamin
T19810	36605-36610	CL_GO_EXT:cell	denotes	cells
T19809	36574-36578	CL_GO_EXT:cell	denotes	cell
T19808	36519-36526	CHEBI:26948	denotes	thiamin
T19807	36379-36386	CHEBI:26948	denotes	thiamin
T19806	36368-36375	CHEBI:26948	denotes	thiamin
T19805	36265-36271	UBERON:0000479	denotes	tissue
T19804	36190-36195	NCBITaxon:9606	denotes	human
T19803	35968-35974	NCBITaxon:9606	denotes	humans
T19802	35864-35870	NCBITaxon:33208	denotes	animal
T19801	35723-35729	NCBITaxon:33208	denotes	animal
T19800	35687-35691	CL_GO_EXT:cell	denotes	cell
T19799	35678-35682	SO_EXT:0000704	denotes	gene
T19798	35621-35628	SO_EXT:0000704	denotes	genetic
T19797	35604-35610	NCBITaxon:33208	denotes	animal
T19796	35551-35557	NCBITaxon:9606	denotes	humans
T19795	35535-35539	SO_EXT:0000704	denotes	gene
T19794	35500-35504	SO_EXT:0000704	denotes	gene
T19793	35475-35480	CL_GO_EXT:cell	denotes	cells
T19792	35460-35480	CL:0002322	denotes	embryonic stem cells
T19791	35460-35469	UBERON:0000922	denotes	embryonic
T19790	35437-35448	CL:0000182	denotes	hepatocytes
T19789	35409-35413	CL_GO_EXT:cell	denotes	cell
T19788	35392-35396	SO_EXT:0000704	denotes	gene
T19787	35343-35348	NCBITaxon:10088	denotes	mouse
T19786	35276-35281	NCBITaxon:9606	denotes	human
T19785	35193-35199	NCBITaxon:39107	denotes	murine
T19784	35125-35131	NCBITaxon:9606	denotes	humans
T19783	35106-35109	NCBITaxon:9913	denotes	cow
T19782	35034-35040	NCBITaxon:33208	denotes	animal
T19781	34910-34913	NCBITaxon:9913	denotes	cow
T19780	34895-34900	NCBITaxon:10088	denotes	mouse
T19779	34858-34862	GO_PR_EXT:branched_chain_amino_acid_aminotransferase	denotes	BCAT
T19778	34721-34729	SO_EXT:sequence_alteration_entity_or_process	denotes	mutation
T19777	34606-34610	CHEBI:22918	denotes	BCAA
T19776	34600-34605	UBERON:0000178	denotes	blood
T19775	34567-34572	NCBITaxon:10088	denotes	mouse
T19774	34552-34558	UBERON_EXT:muscle_structure_or_tissue	denotes	muscle
T19773	34542-34547	UBERON:0002107	denotes	liver
T19772	34505-34509	SO_EXT:0000704	denotes	gene
T19771	34500-34504	GO_PR_EXT:branched_chain_amino_acid_aminotransferase	denotes	BCAT
T19770	34486-34504	PR_EXT:000004683	denotes	mitochondrial BCAT
T19769	34486-34499	GO:0005739	denotes	mitochondrial
T19768	34434-34439	NCBITaxon:9606	denotes	human
T19767	34417-34422	NCBITaxon:10088	denotes	mouse
T19766	34413-34416	CHEBI:23995	denotes	ENU
T19765	34295-34304	GO:0065007	denotes	regulated
T19764	34185-34195	GO:0010467	denotes	expression
T19763	34175-34184	GO:0065007	denotes	regulated
T19762	34141-34151	SO_EXT:0000902	denotes	transgenes
T19761	34117-34133	SO_EXT:0000366	denotes	integration site
T19760	34066-34077	CHEBI:50845	denotes	doxycycline
T19759	33976-33986	SO_EXT:transgenic_entity	denotes	transgenic
T19758	33943-33954	CHEBI:50845	denotes	doxycycline
T19757	33920-33932	CHEBI:27902	denotes	tetracycline
T19756	33897-33905	SO_EXT:0005853	denotes	cassette
T19755	33886-33896	GO:0010467	denotes	expression
T19754	33883-33885	PR_EXT:000006300	denotes	E2
T19753	33877-33882	NCBITaxon:9606	denotes	human
T19752	33813-33822	SO_EXT:0000902	denotes	transgene
T19751	33804-33812	SO_EXT:sequence_rescue_process	denotes	rescuing
T19750	33662-33666	NCBITaxon:10088	denotes	mice
T19749	33522-33526	SO_EXT:0000704	denotes	gene
T19748	33512-33521	GO:0065007	denotes	regulated
T19747	33499-33511	CHEBI:27902	denotes	tetracycline
T19746	33410-33420	SO_EXT:transgenic_entity	denotes	transgenic
T19745	33359-33365	NCBITaxon:33208	denotes	animal
T19744	33329-33333	NCBITaxon:10088	denotes	mice
T19743	33306-33317	SO_EXT:0000704	denotes	genetically
T19742	33284-33289	NCBITaxon:9606	denotes	human
T19741	33272-33276	NCBITaxon:10088	denotes	mice
T19740	33265-33271	SO_EXT:sequence_rescue_process	denotes	rescue
T19739	33158-33162	CHEBI:22918	denotes	BCAA
T19738	33106-33111	NCBITaxon:9606	denotes	human
T19737	33016-33020	NCBITaxon:10088	denotes	mice
T19736	33009-33015	SO_EXT:sequence_rescue_process	denotes	rescue
T19735	32994-32999	UBERON:0000178	denotes	blood
T19734	32979-32983	CHEBI:22918	denotes	BCAA
T19733	32913-32918	UBERON:0002107	denotes	liver
T19732	32858-32863	NCBITaxon:10088	denotes	mouse
T19731	32807-32816	UBERON:0000113	denotes	adulthood
T19730	32790-32794	NCBITaxon:10088	denotes	mice
T19729	32783-32789	SO_EXT:sequence_rescue_process	denotes	rescue
T19728	32760-32769	GO_EXT:fatality_or_lethality	denotes	lethality
T19727	32751-32759	PATO_UBERON_EXT:neonate_or_newborn	denotes	neonatal
T19726	32740-32746	SO_EXT:sequence_rescue_process	denotes	rescue
T19725	32724-32728	NCBITaxon:10088	denotes	mice
T19724	32700-32705	UBERON:0002107	denotes	liver
T19723	32683-32692	SO_EXT:0000902	denotes	transgene
T19722	32680-32682	PR_EXT:000006300	denotes	E2
T19721	32674-32679	NCBITaxon:9606	denotes	human
T19720	32658-32668	GO:0010467	denotes	expression
T19719	32628-32643	UBERON:0007221	denotes	neonatal period
T19718	32607-32610	GO:0016265	denotes	die
T19717	32604-32606	PR_EXT:000006300	denotes	E2
T19716	32586-32595	SO_EXT:0000902	denotes	transgene
T19715	32565-32567	PR_EXT:000006300	denotes	E2
T19714	32539-32543	NCBITaxon:10088	denotes	mice
T19713	32527-32529	PR_EXT:000006300	denotes	E2
T19712	32518-32523	UBERON:0002107	denotes	liver
T19711	32508-32510	PR_EXT:000006300	denotes	E2
T19710	32502-32507	NCBITaxon:9606	denotes	human
T19709	32494-32501	GO:0010467	denotes	express
T19708	32471-32481	SO_EXT:transgenic_entity	denotes	transgenic
T19707	32393-32404	CHEBI_EXT:biochemical	denotes	biochemical
T19706	32355-32360	NCBITaxon:9606	denotes	human
T19705	32261-32266	NCBITaxon:10088	denotes	mouse
T19704	32252-32260	SO_EXT:sequence_alteration_entity_or_process	denotes	mutation
T19703	32247-32251	SO_EXT:sequence_nullness	denotes	null
T19702	32169-32178	CHEBI_GO_SO_EXT:enzyme	denotes	enzymatic
T19701	32121-32125	CHEBI:22918	denotes	BCAA
T19700	32017-32021	NCBITaxon_UBERON_EXT:calf	denotes	calf
T19699	31950-31955	UBERON:0000955	denotes	brain
T19698	31909-31913	CHEBI:22918	denotes	BCAA
T19697	31862-31871	GO_EXT:fatality_or_lethality	denotes	lethality
T19696	31853-31861	PATO_UBERON_EXT:neonate_or_newborn	denotes	neonatal
T19695	31841-31846	GO:0007567	denotes	birth
T19694	31817-31821	GO:0016265	denotes	died
T19693	31812-31816	NCBITaxon_UBERON_EXT:pup	denotes	pups
T19692	31682-31693	CHEBI_SO_EXT:amino_acid	denotes	amino acids
T19691	31643-31650	CHEBI_SO_EXT:alanine	denotes	alanine
T19690	31632-31641	CHEBI_SO_EXT:glutamine	denotes	glutamine
T19689	31621-31630	CHEBI_EXT:glutamate	denotes	glutamate
T19688	31567-31577	UBERON:0001016	denotes	neurologic
T19687	31531-31542	UBERON:0001004	denotes	respiratory
T19686	31511-31516	GO_EXT:biological_movement_or_translocation_process	denotes	motor
T19685	31444-31454	UBERON:0001016	denotes	neurologic
T19684	31390-31397	PATO_UBERON_EXT:neonate_or_newborn	denotes	newborn
T19683	31358-31362	NCBITaxon_UBERON_EXT:pup	denotes	pups
T19682	31352-31357	NCBITaxon:10088	denotes	mouse
T19681	31329-31337	GO_PATO_EXT:biological_behavior	denotes	behavior
T19680	31308-31312	NCBITaxon_UBERON_EXT:pup	denotes	pups
T19679	31282-31293	CL:0000057	denotes	fibroblasts
T19678	31272-31277	UBERON:0002107	denotes	liver
T19677	31250-31257	CHEBI_PR_EXT:protein	denotes	protein
T19676	31247-31249	PR_EXT:000006300	denotes	E2
T19675	31226-31230	CHEBI:22918	denotes	BCAA
T19674	31214-31225	GO:0008152	denotes	metabolized
T19673	31154-31158	NCBITaxon_UBERON_EXT:pup	denotes	pups
T19672	31148-31153	NCBITaxon:10088	denotes	mouse
T19671	31118-31124	UBERON:0002107	denotes	livers
T19670	31061-31065	CHEBI:22918	denotes	BCAA
T19669	31047-31065	GO:0009081	denotes	metabolism of BCAA
T19668	30998-31007	CHEBI_SO_EXT:glutamine	denotes	glutamine
T19667	30983-30992	CHEBI_EXT:glutamate	denotes	glutamate
T19666	30974-30981	CHEBI_SO_EXT:alanine	denotes	alanine
T19665	30962-30973	CHEBI_SO_EXT:amino_acid	denotes	amino acids
T19664	30904-30908	CHEBI:22918	denotes	BCAA
T19663	30888-30893	UBERON:0000178	denotes	blood
T19662	30878-30886	GO:0001967	denotes	suckling
T19661	30858-30863	GO:0007567	denotes	birth
T19660	30835-30840	GO:0007567	denotes	birth
T19659	30781-30785	GO:0007567	denotes	born
T19658	30771-30775	NCBITaxon:10088	denotes	mice
T19657	30736-30742	NCBITaxon:9606	denotes	humans
T19656	30703-30710	NCBITaxon:33208	denotes	animals
T19655	30650-30669	PR_EXT:000006300	denotes	E2 subunit of BCKDH
T19654	30629-30633	SO_EXT:0000704	denotes	gene
T19653	30465-30470	NCBITaxon:10088	denotes	mouse
T19652	30442-30453	SO_EXT:0000704	denotes	genetically
T19651	30306-30312	NCBITaxon:33208	denotes	animal
T15725	30127-30131	NCBITaxon:10088	denotes	mice
T15724	30120-30126	SO_EXT:sequence_rescue_process	denotes	rescue
T15723	29949-29954	UBERON:0002107	denotes	liver
T15722	29926-29932	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T15721	29894-29903	GO:0010467	denotes	expressed
T15720	29816-29823	CHEBI_SO_EXT:alanine	denotes	alanine
T15718	29802-29806	NCBITaxon:10088	denotes	mice
T15717	29742-29746	GO:0016265	denotes	died
T15716	29684-29688	NCBITaxon:10088	denotes	mice
T15715	29556-29566	GO_EXT:killing	denotes	sacrificed
T15714	29514-29518	NCBITaxon:10088	denotes	mice
T15713	29475-29479	NCBITaxon:10088	denotes	mice
T15712	29468-29474	SO_EXT:sequence_rescue_process	denotes	rescue
T15711	29397-29404	NCBITaxon:33208	denotes	animals
T15710	29293-29303	SO_EXT:transgenic_entity	denotes	transgenic
T15709	29273-29277	NCBITaxon:10088	denotes	mice
T15708	29238-29245	UBERON:0000479	denotes	tissues
T15707	29212-29214	PR_EXT:000006300	denotes	E2
T15706	29198-29208	GO:0010467	denotes	expression
T15705	29144-29150	UBERON_EXT:muscle_structure_or_tissue	denotes	muscle
T15704	29133-29139	UBERON:0002113	denotes	kidney
T15703	29126-29131	UBERON:0000955	denotes	brain
T15702	29113-29122	SO_EXT:0000902	denotes	transgene
T15701	29110-29112	PR_EXT:000006300	denotes	E2
T15700	29092-29102	GO:0010467	denotes	expression
T15699	29028-29038	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T15698	29018-29020	PR_EXT:000006300	denotes	E2
T15697	29012-29017	NCBITaxon:10088	denotes	mouse
T15696	28985-28987	PR_EXT:000006300	denotes	E2
T15673	28367-28369	PR_EXT:000006300	denotes	E2
T15672	28349-28358	SO_EXT:0000902	denotes	transgene
T15671	28320-28326	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T15670	28275-28282	CHEBI_PR_EXT:protein	denotes	protein
T15669	28272-28274	PR_EXT:000006300	denotes	E2
T15668	28215-28219	NCBITaxon:10088	denotes	mice
T15667	28196-28206	SO_EXT:transgenic_entity	denotes	transgenic
T15666	28184-28189	UBERON:0002107	denotes	liver
T15665	28160-28162	PR_EXT:000006300	denotes	E2
T15664	28154-28159	NCBITaxon:10088	denotes	mouse
T15663	28110-28112	PR_EXT:000006300	denotes	E2
T15662	28104-28109	NCBITaxon:9606	denotes	human
T15661	28085-28089	NCBITaxon:10088	denotes	mice
T15660	28074-28084	SO_EXT:transgenic_entity	denotes	transgenic
T15659	28051-28055	NCBITaxon:10088	denotes	mice
T15658	28019-28023	NCBITaxon:10088	denotes	mice
T15657	27975-27977	PR_EXT:000006300	denotes	E2
T15656	27969-27974	NCBITaxon:9606	denotes	human
T15655	27917-27922	UBERON:0002107	denotes	liver
T15654	27879-27888	CHEBI_GO_SO_EXT:enzyme	denotes	enzymatic
T15653	27815-27820	UBERON:0002107	denotes	liver
T15652	27793-27802	CHEBI_GO_SO_EXT:enzyme	denotes	enzymatic
T15651	27747-27752	UBERON:0002107	denotes	liver
T15650	27736-27743	CHEBI_PR_EXT:protein	denotes	protein
T15649	27733-27735	PR_EXT:000006300	denotes	E2
T15648	27727-27732	NCBITaxon:9606	denotes	human
T15647	27736-27743	GO:0006412	denotes	protein
T15646	27713-27726	_FRAGMENT	denotes	production of
T15645	27693-27699	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T15644	27670-27680	GO:0010467	denotes	expression
T15643	27655-27660	UBERON:0002107	denotes	liver
T15642	27618-27620	PR_EXT:000006300	denotes	E2
T15641	27612-27617	NCBITaxon:9606	denotes	human
T15640	27601-27611	SO_EXT:transgenic_entity	denotes	transgenic
T15639	27587-27597	GO:0010467	denotes	expression
T15638	27558-27562	NCBITaxon:10088	denotes	mice
T15637	27550-27553	PR_EXT:000005308	denotes	LAP
T15636	26854-26858	NCBITaxon:10088	denotes	mice
T15635	26831-26840	CHEBI_EXT:glutamate	denotes	glutamate
T15634	26818-26822	NCBITaxon:10088	denotes	mice
T15633	26785-26794	CHEBI_SO_EXT:glutamine	denotes	glutamine
T15632	26770-26779	CHEBI_EXT:glutamate	denotes	glutamate
T15631	26761-26768	CHEBI_SO_EXT:alanine	denotes	alanine
T15630	26745-26750	UBERON:0000178	denotes	Blood
T15629	26675-26679	NCBITaxon:10088	denotes	mice
T15628	26664-26674	SO_EXT:transgenic_entity	denotes	transgenic
T15627	26641-26648	CHEBI_SO_EXT:alanine	denotes	alanine
T15626	26636-26640	CHEBI:22918	denotes	BCAA
T15625	26515-26519	NCBITaxon:10088	denotes	mice
T15599	28008-28018	SO_EXT:transgenic_entity	denotes	transgenic
T15598	24805-24809	NCBITaxon_UBERON_EXT:pup	denotes	pups
T15597	24734-24738	NCBITaxon:10088	denotes	mice
T15596	24727-24733	SO_EXT:sequence_rescue_process	denotes	rescue
T15595	24610-24620	SO_EXT:transgenic_entity	denotes	transgenic
T15594	24591-24599	SO_EXT:genotype_or_entity_with_genotype	denotes	genotype
T15593	24584-24590	SO_EXT:sequence_rescue_process	denotes	rescue
T15592	24553-24557	NCBITaxon:10088	denotes	mice
T15591	24501-24511	SO_EXT:0000902	denotes	transgenes
T15590	24467-24469	PR_EXT:000006300	denotes	E2
T15589	24440-24448	SO_EXT:genotype_or_entity_with_genotype	denotes	genotype
T15588	24433-24439	SO_EXT:sequence_rescue_process	denotes	rescue
T15587	24416-24423	NCBITaxon:33208	denotes	animals
T15586	24348-24356	GO_EXT:breeding	denotes	breeding
T15585	24299-24308	GO_EXT:fatality_or_lethality	denotes	lethality
T15584	24290-24298	PATO_UBERON_EXT:neonate_or_newborn	denotes	neonatal
T15583	24265-24271	SO_EXT:sequence_rescue_process	denotes	rescue
T15582	24251-24261	SO_EXT:0000902	denotes	transgenes
T15581	24193-24195	PR_EXT:000006300	denotes	E2
T15580	24174-24183	SO_EXT:0000902	denotes	transgene
T15579	24171-24173	PR_EXT:000006300	denotes	E2
T15578	24152-24161	SO_EXT:0000902	denotes	transgene
T15577	24144-24147	PR_EXT:000005308	denotes	LAP
T15576	24113-24117	NCBITaxon:10088	denotes	mice
T15575	24075-24083	GO_EXT:breeding	denotes	breeding
T15574	24050-24052	PR_EXT:000006300	denotes	E2
T15573	24010-24019	SO_EXT:0000902	denotes	transgene
T15572	24002-24005	PR_EXT:000005308	denotes	LAP
T15571	23970-23974	NCBITaxon:10088	denotes	mice
T15570	23900-23904	NCBITaxon:10088	denotes	mice
T15569	23897-23899	PR_EXT:000006300	denotes	E2
T15568	23882-23892	SO_EXT:transgenic_entity	denotes	Transgenic
T15567	23860-23863	CHEBI_SO_EXT:DNA	denotes	DNA
T15566	23855-23859	UBERON:0002415	denotes	tail
T15540	23028-23032	NCBITaxon:10088	denotes	mice
T15539	23020-23023	PR_EXT:000005308	denotes	LAP
T15538	21700-21708	SO_EXT:0000167	denotes	promoter
T15537	21665-21669	SO_EXT:cDNA	denotes	cDNA
T15536	21662-21664	PR_EXT:000006300	denotes	E2
T15535	21656-21661	NCBITaxon:9606	denotes	human
T15534	21646-21653	GO:0010467	denotes	express
T15533	21620-21629	SO_EXT:0000902	denotes	transgene
T15532	21617-21619	PR_EXT:000006300	denotes	E2
T15531	21585-21593	GO_EXT:reaction_or_response	denotes	response
T15530	21546-21555	SO_EXT:0000167	denotes	promoters
T15529	21532-21542	GO:0010467	denotes	expression
T15528	21495-21515	GO_EXT:transcription_factor	denotes	transcription factor
T15527	21495-21508	GO_EXT:transcription	denotes	transcription
T15526	21460-21470	GO:0065007	denotes	controlled
T15525	21447-21459	CHEBI:27902	denotes	tetracycline
T15524	21429-21439	GO:0010467	denotes	expression
T15523	21414-21419	UBERON:0002107	denotes	liver
T15522	21391-21398	GO_EXT:biological_direction_or_guidance	denotes	directs
T15521	21376-21385	SO_EXT:0000902	denotes	transgene
T15520	21368-21371	PR_EXT:000005308	denotes	LAP
T15519	21343-21352	SO_EXT:0000902	denotes	transgene
T15518	21340-21342	PR_EXT:000006300	denotes	E2
T15517	21320-21329	SO_EXT:0000902	denotes	transgene
T15516	21312-21315	PR_EXT:000005308	denotes	LAP
T15515	21279-21289	SO_EXT:transgenic_entity	denotes	transgenic
T15514	21247-21249	PR_EXT:000006300	denotes	E2
T15513	21234-21239	UBERON:0002107	denotes	liver
T15695	28979-28984	NCBITaxon:9606	denotes	Human
T15694	28966-28977	PR_EXT:000006506	denotes	E3 subunits
T15693	28953-28958	NCBITaxon:10088	denotes	mouse
T15692	28938-28947	GO:0032991	denotes	complexed
T15691	28905-28907	PR_EXT:000006300	denotes	E2
T15690	28899-28904	NCBITaxon:9606	denotes	human
T15689	28851-28867	GO:0065003	denotes	subunit assembly
T15688	28812-28819	NCBITaxon:562	denotes	E. coli
T15687	28779-28795	CHEBI_SO_EXT:C_terminus_or_C_terminal_region	denotes	carboxy terminus
T15686	28768-28771	CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag	denotes	tag
T15685	28747-28756	SO_EXT:sequence_insertion_entity_or_process	denotes	insertion
T15684	28669-28699	GO:0045254	denotes	pyruvate dehydrogenase complex
T15683	28669-28691	GO_EXT:0004738	denotes	pyruvate dehydrogenase
T15682	28669-28677	CHEBI:15361	denotes	pyruvate
T15681	28621-28637	CHEBI_SO_EXT:C_terminus_or_C_terminal_region	denotes	carboxy terminus
T15680	28516-28525	CHEBI_GO_SO_EXT:enzyme	denotes	enzymatic
T15679	28497-28499	PR_EXT:000006300	denotes	E2
T15678	28491-28496	NCBITaxon:9606	denotes	human
T15677	28473-28482	SO_EXT:0000902	denotes	transgene
T15676	28449-28465	CHEBI_SO_EXT:C_terminus_or_C_terminal_region	denotes	carboxy terminus
T15675	28438-28441	CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag	denotes	tag
T15674	28432-28437	PR_EXT:000000084	denotes	c-myc
T12205	20810-20814	NCBITaxon:10088	denotes	mice
T12204	20798-20800	PR_EXT:000006300	denotes	E2
T12203	20754-20760	NCBITaxon:9606	denotes	humans
T12202	20683-20692	GO_EXT:fatality_or_lethality	denotes	lethality
T12201	20674-20682	PATO_UBERON_EXT:neonate_or_newborn	denotes	neonatal
T12200	20630-20639	GO:0008152	denotes	metabolic
T12199	20617-20622	UBERON:0001088	denotes	urine
T12198	20607-20612	UBERON:0000178	denotes	blood
T12197	20595-20599	CHEBI:22918	denotes	BCAA
T12196	20537-20539	PR_EXT:000006300	denotes	E2
T12195	20517-20526	CHEBI_GO_SO_EXT:enzyme	denotes	enzymatic
T12194	20501-20505	NCBITaxon:10088	denotes	mice
T12193	20489-20491	PR_EXT:000006300	denotes	E2
T3189	240-250	CHEBI:25754	denotes	keto acids
T3190	264-290	CHEBI:22918	denotes	branched-chain amino acids
T3191	279-290	CHEBI_SO_EXT:amino_acid	denotes	amino acids
T3192	292-296	CHEBI:22918	denotes	BCAA
T3193	299-306	CHEBI_SO_EXT:leucine	denotes	leucine
T3194	308-318	CHEBI_SO_EXT:isoleucine	denotes	isoleucine
T3195	323-329	CHEBI_SO_EXT:valine	denotes	valine
T3196	391-399	SO_EXT:sequence_alteration_entity_or_process	denotes	mutation
T3197	426-432	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T3198	674-678	CHEBI:22918	denotes	BCAA
T3199	682-687	UBERON:0000178	denotes	blood
T3200	698-709	UBERON:0006314	denotes	body fluids
T3201	986-990	CHEBI:22918	denotes	BCAA
T3202	1120-1125	UBERON:0000178	denotes	blood
T3203	1126-1130	CHEBI:22918	denotes	BCAA
T3204	1357-1370	GO:0017086	denotes	BCKDH complex
T3205	1386-1392	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T3206	1420-1429	GO_MOP_EXT:catalysis	denotes	catalytic
T3207	1430-1438	CHEBI_PR_EXT:protein	denotes	proteins
T3208	1442-1455	GO_EXT:0016831	denotes	decarboxylase
T3209	1464-1477	CHEBI:50488	denotes	dihydrolipoyl
T3210	1464-1490	GO_PR_EXT:dihydrolipoyllysine_residue_2_methylpropanoyl_transferase	denotes	dihydrolipoyl transacylase
T3211	1492-1494	PR_EXT:000006300	denotes	E2
T3212	1503-1516	CHEBI:50488	denotes	dihydrolipoyl
T3213	1503-1530	GO_PR_EXT:dihydrolipoamide_dehydrogenase	denotes	dihydrolipoyl dehydrogenase
T3214	1532-1534	PR_EXT:000006506	denotes	E3
T3215	1565-1573	GO_EXT:tetrameric_macromolecular_complex	denotes	tetramer
T3216	1590-1591	_FRAGMENT	denotes	α
T3217	1602-1610	PR_EXT:000004686	denotes	subunits
T3218	1600-1610	PR_EXT:000004687	denotes	β subunits
T3219	1627-1629	PR_EXT:000006300	denotes	E2
T3220	1672-1674	PR_EXT:000006506	denotes	E3
T3221	1691-1699	CHEBI:15361	denotes	pyruvate
T3222	1691-1699	_FRAGMENT	denotes	pyruvate
T3223	1720-1733	GO_EXT:0004738	denotes	dehydrogenase
T3224	1720-1743	GO:0045254	denotes	dehydrogenase complexes
T3225	1704-1719	CHEBI_EXT:2_oxoglutarate	denotes	α-ketoglutarate
T3226	1704-1733	GO_EXT:0004591	denotes	α-ketoglutarate dehydrogenase
T3227	1704-1743	GO:0045240	denotes	α-ketoglutarate dehydrogenase complexes
T3228	1756-1763	CHEBI_SO_EXT:glycine	denotes	glycine
T3229	1756-1779	GO:0005960	denotes	glycine cleavage system
T3230	1764-1772	MOP:0000780	denotes	cleavage
T3231	1819-1829	GO:0065007	denotes	regulatory
T3232	1830-1838	CHEBI_PR_EXT:protein	denotes	proteins
T3233	1851-1857	GO_EXT:0016301	denotes	kinase
T3234	1864-1875	GO_EXT:0016791	denotes	phosphatase
T3235	1882-1890	GO:0065007	denotes	regulate
T3236	1912-1918	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T3237	1929-1944	GO_PATO_EXT:phosphorylation_process	denotes	phosphorylation
T3238	1964-1981	GO:0016311	denotes	dephosphorylation
T3239	2008-2020	PR_EXT:000004686	denotes	E1 α subunit
T3240	2028-2037	SO_EXT:sequence_alteration_entity_or_process	denotes	Mutations
T3241	2045-2050	SO_EXT:0000704	denotes	genes
T3242	2065-2085	PR_EXT:000006300	denotes	E2 subunits of BCKDH
T3243	2137-2146	SO_EXT:sequence_alteration_entity_or_process	denotes	mutations
T3244	2178-2188	PR_EXT:000006300	denotes	E2 subunit
T3245	2264-2274	GO:0065007	denotes	regulatory
T3246	2275-2281	GO_EXT:0016301	denotes	kinase
T3247	2286-2297	GO_EXT:0016791	denotes	phosphatase
T3248	2390-2397	CHEBI_PR_EXT:protein	denotes	protein
T3249	2401-2405	CHEBI:22918	denotes	BCAA
T3250	2516-2525	GO:0008152	denotes	metabolic
T3251	2780-2785	UBERON:0002107	denotes	liver
T3252	2789-2799	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T3253	2789-2810	GO:0006520	denotes	amino acid metabolism
T3254	2857-2862	NCBITaxon:9606	denotes	human
T3255	2863-2868	UBERON:0002107	denotes	liver
T3256	2928-2933	UBERON:0002107	denotes	liver
T3257	2991-2996	UBERON:0002107	denotes	liver
T3258	3128-3145	CHEBI_EXT:35705	denotes	immunosuppressant
T3259	3146-3151	CHEBI_EXT:23888	denotes	drugs
T3260	3253-3258	UBERON:0002107	denotes	liver
T3261	3305-3311	UBERON:0002107	denotes	livers
T3262	3615-3621	NCBITaxon:33208	denotes	animal
T3263	3690-3694	NCBITaxon_UBERON_EXT:calf	denotes	calf
T3264	3857-3863	NCBITaxon:33208	denotes	animal
T3265	3875-3880	NCBITaxon:9606	denotes	human
T3266	3962-3968	NCBITaxon:33208	denotes	animal
T3267	4000-4005	NCBITaxon:9606	denotes	human
T3268	4027-4048	CHEBI:23995	denotes	N-ethyl-N-nitrosourea
T3269	4050-4053	CHEBI:23995	denotes	ENU
T3270	4063-4069	SO_EXT:sequence_altered_entity_or_alteration_process	denotes	mutant
T3271	4070-4075	NCBITaxon:10088	denotes	mouse
T3272	4106-4111	NCBITaxon:9606	denotes	human
T3273	4155-4163	SO_EXT:sequence_alteration_entity_or_process	denotes	mutation
T3274	4189-4195	GO:0008380	denotes	splice
T3275	4189-4200	SO_EXT:0000162	denotes	splice site
T3276	4208-4221	GO:0005739	denotes	mitochondrial
T3277	4208-4253	PR_EXT:000004683	denotes	mitochondrial branched-chain aminotransferase
T3278	4222-4253	GO_PR_EXT:branched_chain_amino_acid_aminotransferase	denotes	branched-chain aminotransferase
T3279	4255-4259	GO_PR_EXT:branched_chain_amino_acid_aminotransferase	denotes	BCAT
T3280	4261-4265	SO_EXT:0000704	denotes	gene
T3281	4295-4301	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T3282	4323-4331	SO_EXT:sequence_alteration_entity_or_process	denotes	mutation
T3283	4370-4376	SO_EXT:sequence_altered_entity_or_alteration_process	denotes	mutant
T3284	4377-4382	NCBITaxon:10088	denotes	mouse
T3285	4401-4406	NCBITaxon:9606	denotes	human
T3286	4478-4489	SO_EXT:0000704	denotes	genetically
T3287	4501-4507	NCBITaxon:39107	denotes	murine
T3288	4601-4606	NCBITaxon:9606	denotes	human
T3289	4678-4697	PR_EXT:000006300	denotes	E2 subunit of BCKDH
T3290	4712-4725	GO_SO_EXT:sequence_rearrangement_process	denotes	recombination
T4357	5111-5118	NCBITaxon:33208	denotes	animals
T4358	5194-5200	NCBITaxon:33208	denotes	Animal
T4968	5226-5230	SO_EXT:0000704	denotes	Gene
T4969	5253-5264	SO_EXT:genomic_DNA	denotes	genomic DNA
T4970	5261-5264	CHEBI_SO_EXT:DNA	denotes	DNA
T4971	5292-5295	CHEBI_SO_EXT:DNA	denotes	DNA
T4972	5313-5329	SO_EXT:0000852	denotes	portion of Exons
T4973	5345-5347	PR_EXT:000006300	denotes	E2
T4974	5348-5352	SO_EXT:0000704	denotes	gene
T4975	5357-5365	SO:0000357	denotes	flanking
T4976	5366-5369	CHEBI_SO_EXT:DNA	denotes	DNA
T4977	5390-5398	NCBITaxon:10678	denotes	P1 phage
T4978	5412-5418	SO_EXT:0001026	denotes	Genome
T4979	5457-5462	NCBITaxon:10088	denotes	Mouse
T4980	5463-5465	CL:0002322	denotes	ES
T4981	5497-5508	SO_EXT:sequence_substitution_entity_or_process	denotes	replacement
T4982	5514-5518	SO_EXT:0000704	denotes	gene
T4983	5519-5535	SO_EXT:0001644	denotes	targeting vector
T4984	5556-5565	SO_EXT:sequence_substitution_process	denotes	replacing
T4985	5574-5575	CHEBI_SO_EXT:base	denotes	b
T4986	5612-5627	SO_EXT:0000852	denotes	portion of Exon
T4987	5641-5645	SO_EXT:0000147	denotes	Exon
T4988	5664-5670	CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag	denotes	marker
T4989	5671-5675	SO_EXT:0000704	denotes	gene
T4990	5704-5710	SO_EXT:0000440	denotes	vector
T4991	5731-5740	SO_EXT:engineered_biological_sequence	denotes	construct
T4992	5745-5755	SO_EXT:sequence_linearization	denotes	linearized
T4993	5793-5801	CL:0002322	denotes	ES cells
T4994	5796-5801	CL_GO_EXT:cell	denotes	cells
T4995	5851-5859	CL:0002322	denotes	ES cells
T4996	5854-5859	CL_GO_EXT:cell	denotes	cells
T4997	5879-5883	CHEBI:42768	denotes	G418
T4998	5896-5900	UBERON:0000104	denotes	Life
T4999	5942-5953	CHEBI:465284	denotes	gancyclovir
T5000	6010-6016	SO_EXT:sequence_cloned_entity	denotes	clones
T5001	6035-6039	SO_EXT:0000704	denotes	gene
T5002	6093-6104	SO_EXT:genomic_DNA	denotes	genomic DNA
T5003	6101-6104	CHEBI_SO_EXT:DNA	denotes	DNA
T5004	6117-6127	GO:0097617	denotes	hybridized
T5005	6136-6140	SO_EXT:0000147	denotes	Exon
T5006	6152-6157	CHEBI_SO_EXT:molecular_probe	denotes	probe
T5007	6183-6187	SO_EXT:0000704	denotes	gene
T5008	6198-6207	SO_EXT:engineered_biological_sequence	denotes	construct
T5009	6228-6236	CL:0002322	denotes	ES cells
T5010	6231-6236	CL_GO_EXT:cell	denotes	cells
T5011	6265-6276	UBERON:0000358	denotes	blastocysts
T5012	6297-6301	NCBITaxon:10088	denotes	mice
T5013	6414-6423	SO_EXT:wild_type_entity_or_quality	denotes	wild type
T5014	6425-6426	SO_EXT:normal_or_wild_type_or_present	denotes	+
T5015	6427-6428	SO_EXT:normal_or_wild_type_or_present	denotes	+
T5016	6445-6446	SO_EXT:normal_or_wild_type_or_present	denotes	+
T5017	6447-6448	SO_EXT:sequence_nullness_or_absence	denotes	-
T5018	6475-6476	SO_EXT:sequence_nullness_or_absence	denotes	-
T5019	6477-6478	SO_EXT:sequence_nullness_or_absence	denotes	-
T5020	6480-6484	NCBITaxon:10088	denotes	mice
T5021	6506-6507	SO_EXT:normal_or_wild_type_or_present	denotes	+
T5022	6508-6509	SO_EXT:sequence_nullness_or_absence	denotes	-
T5023	6510-6518	GO_EXT:breeding	denotes	breeding
T5024	6568-6572	NCBITaxon:10088	denotes	mice
T5025	6611-6618	NCBITaxon:33208	denotes	animals
T5026	6663-6670	SO_EXT:0000704	denotes	genetic
T5818	8178-8188	SO_EXT:transgenic_entity	denotes	transgenic
T5819	8189-8193	NCBITaxon:10088	denotes	mice
T5820	8203-8212	CHEBI_EXT:polyatomic_entity_or_group	denotes	molecular
T5821	8250-8260	SO_EXT:transgenic_entity	denotes	transgenic
T5822	8261-8270	SO_EXT:engineered_biological_sequence	denotes	construct
T5823	8277-8279	PR_EXT:000006300	denotes	E2
T5824	8286-8295	SO_EXT:0000902	denotes	transgene
T5825	8309-8321	CHEBI:27902	denotes	tetracycline
T5826	8333-8337	NCBITaxon:10359	denotes	hCMV
T5827	8341-8349	SO_EXT:0000167	denotes	promoter
T5828	8369-8381	CHEBI:27902	denotes	tetracycline
T5829	8421-8425	NCBITaxon:10359	denotes	hCMV
T5830	8426-8434	SO_EXT:0000167	denotes	promoter
T5831	8494-8500	SO_EXT:0000188	denotes	intron
T5832	8532-8539	SO_EXT:0000673	denotes	message
T5833	8532-8539	CHEBI:33695	denotes	message
T5834	8554-8564	GO:0010467	denotes	expression
T5835	8582-8591	SO:0000993	denotes	consensus
T5836	8592-8600	SO_EXT:biological_sequence	denotes	sequence
T5837	8608-8624	SO_EXT:0000318	denotes	initiation codon
T5838	8637-8648	GO:0006412	denotes	translation
T5839	8659-8664	NCBITaxon:9606	denotes	human
T5840	8665-8667	PR_EXT:000006300	denotes	E2
T5841	8668-8672	SO_EXT:cDNA	denotes	cDNA
T5842	8688-8696	SO_EXT:sequence_alteration_process	denotes	modified
T5843	8713-8720	CHEBI_SO_EXT:alanine	denotes	alanine
T5844	8742-8747	PR_EXT:000000084	denotes	c-myc
T5845	8748-8755	CHEBI_SO_EXT:epitope	denotes	epitope
T5846	8756-8759	CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag	denotes	tag
T5847	8767-8783	CHEBI_SO_EXT:C_terminus_or_C_terminal_region	denotes	carboxy terminus
T5848	8816-8820	NCBITaxon:10633	denotes	SV40
T5849	8826-8841	GO:0043631	denotes	polyadenylation
T5850	8826-8850	SO_EXT:0000610	denotes	polyadenylation sequence
T5851	8873-8877	CHEBI_SO_EXT:mRNA	denotes	mRNA
T5852	8892-8903	GO:0006412	denotes	translation
T5853	8915-8916	CHEBI_SO_EXT:base	denotes	b
T5854	8921-8923	PR_EXT:000006300	denotes	E2
T5855	8924-8933	SO_EXT:0000902	denotes	transgene
T5856	8952-8958	SO_EXT:0000440	denotes	vector
T5857	8959-8968	SO_EXT:biological_sequence	denotes	sequences
T5858	9003-9008	PR_EXT:P23940	denotes	BamHI
T5859	9065-9070	NCBITaxon:10088	denotes	mouse
T5860	9071-9078	UBERON:0000922	denotes	embryos
T5861	9086-9096	SO_EXT:transgenic_entity	denotes	transgenic
T5862	9193-9204	SO_EXT:genomic_DNA	denotes	Genomic DNA
T5863	9201-9204	CHEBI_SO_EXT:DNA	denotes	DNA
T5864	9214-9218	UBERON:0002415	denotes	tail
T5865	9222-9226	NCBITaxon:10088	denotes	mice
T5866	9301-9314	GO:0097617	denotes	hybridization
T5867	9326-9328	SO_EXT:0000028	denotes	bp
T5868	9329-9334	CHEBI_SO_EXT:molecular_probe	denotes	probe
T5869	9352-9356	NCBITaxon:10633	denotes	SV40
T5870	9376-9378	PR_EXT:000006300	denotes	E2
T5871	9379-9388	SO_EXT:0000902	denotes	transgene
T6401	9423-9429	NCBITaxon:39107	denotes	murine
T6402	9452-9454	PR_EXT:000006300	denotes	E2
T6403	9455-9465	SO_EXT:transgenic_entity	denotes	transgenic
T6404	9486-9491	GO:0007618	denotes	mated
T6405	9509-9513	NCBITaxon:10088	denotes	mice
T6406	9550-9552	PR_EXT:000006300	denotes	E2
T6407	9570-9573	PR_EXT:000005308	denotes	LAP
T6408	9578-9587	SO_EXT:0000902	denotes	transgene
T6409	9589-9591	SO_EXT:transgenic_entity	denotes	Tg
T6410	9698-9706	GO_EXT:breeding	denotes	breeding
T6411	9710-9717	NCBITaxon:33208	denotes	animals
T6412	9750-9760	SO_EXT:0000902	denotes	transgenes
T6413	9808-9812	NCBITaxon:10088	denotes	mice
T6414	9831-9840	SO_EXT:genotype_or_entity_with_genotype	denotes	genotypes
T6415	9856-9863	NCBITaxon:33208	denotes	animals
T6416	9929-9939	SO_EXT:0000902	denotes	transgenes
T6417	9958-9966	SO_EXT:genotype_or_entity_with_genotype	denotes	genotype
T6418	9975-9981	SO_EXT:sequence_rescue_process	denotes	rescue
T6419	9983-9991	SO_EXT:genotype_or_entity_with_genotype	denotes	genotype
T6420	10014-10022	SO_EXT:sequence_rescue_process	denotes	rescuing
T6421	10027-10035	PATO_UBERON_EXT:neonate_or_newborn	denotes	neonatal
T6422	10036-10042	GO_EXT:fatality_or_lethality	denotes	lethal
T6423	10117-10124	NCBITaxon:33208	denotes	animals
T6424	10139-10149	SO_EXT:0000902	denotes	transgenes
T6425	10175-10190	UBERON:0007221	denotes	neonatal period
T6662	10208-10212	NCBITaxon:10088	denotes	mice
T6663	10255-10267	SO_EXT:genomic_DNA	denotes	Genomic DNAs
T6664	10263-10267	CHEBI_SO_EXT:DNA	denotes	DNAs
T6665	10282-10286	UBERON:0002415	denotes	tail
T6666	10327-10345	GO_EXT:0015666	denotes	restriction enzyme
T6667	10339-10345	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T6668	10368-10375	CHEBI:2511	denotes	agarose
T6669	10408-10413	CHEBI:25614	denotes	nylon
T7154	10483-10488	NCBITaxon:10088	denotes	mouse
T7155	10489-10498	UBERON:0000922	denotes	embryonic
T7156	10499-10510	CL:0000057	denotes	fibroblasts
T7157	10530-10539	UBERON:0000922	denotes	embryonic
T7158	10582-10593	CL:0000057	denotes	Fibroblasts
T7159	10630-10646	CHEBI_EXT:paraformaldehye	denotes	paraformaldehyde
T7160	10690-10706	CHEBI_EXT:paraformaldehye	denotes	paraformaldehyde
T7161	10723-10734	CHEBI:9750	denotes	Triton X100
T7162	10810-10817	CHEBI_SO_EXT:glycine	denotes	glycine
T7163	10827-10833	CHEBI_CHMO_EXT:buffer_solution	denotes	Buffer
T7164	10882-10886	NCBITaxon:9925	denotes	goat
T7165	10887-10890	GO:0071735	denotes	IgG
T7166	10944-10950	CHEBI_CHMO_EXT:buffer_solution	denotes	Buffer
T7167	10954-10959	CL_GO_EXT:cell	denotes	cells
T7168	10991-10993	PR_EXT:000006300	denotes	E2
T7169	11007-11012	UBERON:0001977	denotes	serum
T7170	11057-11063	CHEBI_CHMO_EXT:buffer_solution	denotes	Buffer
T7171	11108-11115	CHEBI_SO_EXT:molecular_label_or_mark_or_tag_process	denotes	labeled
T7172	11123-11131	GO:0042571	denotes	antibody
T7173	11149-11154	CL_GO_EXT:cell	denotes	cells
T7174	11198-11204	CHEBI_CHMO_EXT:buffer_solution	denotes	Buffer
T7175	11227-11235	CHEBI_EXT:poly_vinyl_alcohol	denotes	gelvatol
T7176	11263-11269	UBERON:0002107	denotes	livers
T7177	11275-11282	PATO_UBERON_EXT:neonate_or_newborn	denotes	newborn
T7178	11283-11287	NCBITaxon_UBERON_EXT:pup	denotes	pups
T7179	11335-11351	CHEBI_EXT:paraformaldehye	denotes	paraformaldehyde
T7180	11408-11416	CHEBI_EXT:nitrogen	denotes	nitrogen
T7181	11424-11434	CHEBI:30362	denotes	isopentane
T7182	11499-11504	CL_GO_EXT:cell	denotes	cells
T7534	11562-11572	CHEBI_SO_EXT:amino_acid	denotes	Amino acid
T7535	11582-11587	UBERON:0000178	denotes	Blood
T7536	11624-11629	UBERON:0001825	denotes	sinus
T7537	11633-11642	UBERON:0003481	denotes	tail vein
T7538	11646-11650	NCBITaxon:10088	denotes	mice
T7539	11700-11705	UBERON:0000178	denotes	blood
T7540	11706-11716	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T7541	11733-11738	GO:0007567	denotes	natal
T7542	11768-11772	CHEBI:22918	denotes	BCAA
T7543	11783-11794	CHEBI_SO_EXT:amino_acid	denotes	amino acids
T7544	11798-11803	UBERON:0000178	denotes	blood
T8070	11913-11919	UBERON:0002107	denotes	Livers
T8071	11951-11959	CHEBI_EXT:nitrogen	denotes	nitrogen
T8072	11997-12003	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T8073	12011-12017	UBERON:0002107	denotes	livers
T8074	12068-12075	CHEBI:17992	denotes	sucrose
T8075	12083-12087	CHEBI:9754	denotes	Tris
T8076	12088-12091	CHEBI:17883	denotes	HC1
T8077	12101-12106	UBERON:0002107	denotes	Liver
T8078	12248-12254	UBERON:0000479	denotes	tissue
T8079	12315-12320	UBERON:0002107	denotes	liver
T8080	12321-12327	UBERON:0000479	denotes	tissue
T8081	12347-12354	PATO_UBERON_EXT:neonate_or_newborn	denotes	newborn
T8082	12355-12359	NCBITaxon_UBERON_EXT:pup	denotes	pups
T8083	12408-12415	GO_EXT:biological_release	denotes	release
T8084	12421-12424	CHEBI:16526	denotes	CO2
T8085	12430-12436	_FRAGMENT	denotes	α-keto
T8086	12445-12456	CHEBI:17865	denotes	isocaproate
T8087	12440-12443	CHEBI:36927	denotes	14C
T8088	12509-12516	CHEBI:60004	denotes	mixture
T8089	12553-12572	CHEBI_EXT:potassium_phosphate	denotes	potassium phosphate
T8090	12573-12579	CHEBI_CHMO_EXT:buffer_solution	denotes	buffer
T8091	12597-12614	CHEBI:17865	denotes	α-ketoisocaproate
T8092	12624-12629	CHEBI:15346	denotes	CoASH
T8093	12639-12660	CHEBI:9532	denotes	thiamin pyrophosphate
T8094	12667-12671	CHEBI:15846	denotes	NAD+
T8095	12678-12692	CHEBI:18320	denotes	dithiothreitol
T8096	12699-12703	CHEBI:18420	denotes	Mg2+
T8097	12734-12740	_FRAGMENT	denotes	α-keto
T8098	12749-12760	CHEBI:17865	denotes	isocaproate
T8099	12744-12747	CHEBI:36927	denotes	14C
T8100	12777-12782	UBERON:0002107	denotes	liver
T8101	12802-12809	CHEBI_PR_EXT:protein	denotes	protein
T8102	12858-12861	CHEBI:16526	denotes	CO2
T8103	12877-12886	CHEBI:24651	denotes	hydroxide
T8104	12890-12897	CHEBI:31264	denotes	Hyamine
T8787	12993-13000	CHEBI_PR_EXT:protein	denotes	Protein
T8788	13041-13046	UBERON:0002107	denotes	liver
T8789	13087-13095	SO_EXT:wild_type_entity_or_quality	denotes	wildtype
T8790	13119-13129	SO_EXT:transgenic_entity	denotes	transgenic
T8791	13130-13134	NCBITaxon:10088	denotes	mice
T8792	13136-13143	CHEBI_PR_EXT:protein	denotes	Protein
T8793	13204-13207	CHEBI:8984	denotes	SDS
T8794	13251-13262	GO_EXT:biological_movement_or_translocation_process	denotes	transferred
T8795	13266-13270	CHEBI:53250	denotes	PVDF
T8796	13349-13351	PR_EXT:000006300	denotes	E2
T8797	13352-13359	CHEBI_PR_EXT:protein	denotes	protein
T8798	13377-13383	NCBITaxon:9986	denotes	rabbit
T8799	13384-13386	PR_EXT:000006300	denotes	E2
T8800	13391-13395	UBERON:0001977	denotes	sera
T8801	13426-13431	NCBITaxon:10088	denotes	mouse
T8802	13445-13450	NCBITaxon:9606	denotes	human
T8803	13460-13471	PR_EXT:000006300	denotes	E2 subunits
T8804	13560-13566	NCBITaxon:9986	denotes	rabbit
T8805	13572-13577	PR_EXT:000000084	denotes	c-myc
T8806	13578-13581	CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag	denotes	tag
T8807	13582-13590	GO:0042571	denotes	antibody
T8808	13677-13685	GO:0042571	denotes	antibody
T8809	13690-13697	PR_EXT:000003676	denotes	β-actin
T8810	13776-13780	NCBITaxon:9925	denotes	goat
T8811	13786-13792	NCBITaxon:9986	denotes	rabbit
T8812	13803-13811	GO:0042571	denotes	antibody
T8813	13812-13822	MOP:0000779	denotes	conjugated
T8814	13826-13837	NCBITaxon:3704	denotes	horseradish
T8815	13838-13848	GO_EXT:0004601	denotes	peroxidase
T8816	13966-13973	CHEBI_EXT:33893	denotes	reagent
T9138	14054-14058	CHEBI:22918	denotes	BCAA
T9139	14069-14075	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T9140	14181-14190	SO_EXT:genotype_or_entity_with_genotype	denotes	genotypes
T10230	14254-14256	PR_EXT:000006300	denotes	E2
T10231	14257-14261	SO_EXT:0000704	denotes	gene
T10232	14271-14275	NCBITaxon:10088	denotes	mice
T10233	14286-14288	PR_EXT:000006300	denotes	E2
T10234	14298-14302	NCBITaxon:10088	denotes	mice
T10235	14312-14316	SO_EXT:0000704	denotes	gene
T10236	14330-14335	NCBITaxon:10088	denotes	mouse
T10237	14336-14344	CL:0002322	denotes	ES cells
T10238	14339-14344	CL_GO_EXT:cell	denotes	cells
T10239	14360-14362	PR_EXT:000006300	denotes	E2
T10240	14363-14367	SO_EXT:0000704	denotes	gene
T10241	14409-14411	PR_EXT:000006300	denotes	E2
T10242	14412-14416	SO_EXT:0000704	denotes	gene
T10243	14448-14452	SO_EXT:0000704	denotes	gene
T10244	14463-14472	SO_EXT:engineered_biological_sequence	denotes	construct
T10245	14489-14496	SO_EXT:sequence_substitution_process	denotes	replace
T10246	14505-14506	CHEBI_SO_EXT:base	denotes	b
T10247	14518-14529	SO_EXT:genomic_DNA	denotes	genomic DNA
T10248	14526-14529	CHEBI_SO_EXT:DNA	denotes	DNA
T10249	14552-14564	SO_EXT:0000852	denotes	part of Exon
T10250	14578-14582	SO_EXT:0000147	denotes	Exon
T10251	14612-14618	CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag	denotes	marker
T10252	14636-14643	CL:0002322	denotes	ES cell
T10253	14639-14643	CL_GO_EXT:cell	denotes	cell
T10254	14644-14650	SO_EXT:sequence_cloned_entity	denotes	clones
T10255	14733-14774	SO_EXT:0000193	denotes	restriction fragment length polymorphisms
T10256	14789-14793	SO_EXT:0000704	denotes	gene
T10257	14811-14813	PR_EXT:000006300	denotes	E2
T10258	14858-14860	PR_EXT:000006300	denotes	E2
T10259	14861-14865	SO_EXT:0000147	denotes	Exon
T10260	14877-14882	CHEBI_SO_EXT:molecular_probe	denotes	probe
T10261	14919-14928	SO_EXT:engineered_biological_sequence	denotes	construct
T10262	14930-14940	GO:0097617	denotes	hybridizes
T10263	14956-14957	CHEBI_SO_EXT:base	denotes	b
T10264	14963-14983	SO_EXT:0000412	denotes	restriction fragment
T10265	14993-15002	SO_EXT:wild_type_entity_or_quality	denotes	wild type
T10266	15003-15009	SO_EXT:0001023	denotes	allele
T10267	15029-15036	CL:0002322	denotes	ES cell
T10268	15032-15036	CL_GO_EXT:cell	denotes	cell
T10269	15065-15073	CL:0002322	denotes	ES cells
T10270	15068-15073	CL_GO_EXT:cell	denotes	cells
T10271	15080-15085	CHEBI_SO_EXT:molecular_probe	denotes	probe
T10272	15091-15101	GO:0097617	denotes	hybridizes
T10273	15112-15113	CHEBI_SO_EXT:base	denotes	b
T10274	15119-15139	SO_EXT:0000412	denotes	restriction fragment
T10275	15189-15208	GO_EXT:0015666	denotes	restriction enzymes
T10276	15201-15208	CHEBI_GO_SO_EXT:enzyme	denotes	enzymes
T10277	15213-15219	CHEBI_SO_EXT:molecular_probe	denotes	probes
T10278	15257-15265	CL:0002322	denotes	ES cells
T10279	15260-15265	CL_GO_EXT:cell	denotes	cells
T10280	15290-15301	UBERON:0000358	denotes	blastocysts
T10281	15322-15326	NCBITaxon:10088	denotes	mice
T10282	15343-15347	GO_EXT:breeding	denotes	bred
T10283	15360-15364	NCBITaxon:10088	denotes	mice
T10284	15414-15420	SO_EXT:0001023	denotes	allele
T10285	15435-15439	NCBITaxon:10088	denotes	mice
T10286	15450-15454	GO_EXT:breeding	denotes	bred
T10287	15466-15475	SO_EXT:wild_type_entity_or_quality	denotes	wild type
T10288	15477-15478	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10289	15479-15480	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10290	15497-15498	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10291	15499-15500	SO_EXT:sequence_nullness_or_absence	denotes	-
T10292	15518-15519	SO_EXT:sequence_nullness_or_absence	denotes	-
T10293	15520-15521	SO_EXT:sequence_nullness_or_absence	denotes	-
T10294	15523-15530	NCBITaxon:33208	denotes	animals
T10295	15532-15536	NCBITaxon:10088	denotes	Mice
T10296	15583-15587	SO_EXT:0000147	denotes	Exon
T10297	15599-15604	CHEBI_SO_EXT:molecular_probe	denotes	probe
T10298	15605-15615	GO:0097617	denotes	hybridized
T10299	15631-15632	CHEBI_SO_EXT:base	denotes	b
T10300	15638-15658	SO_EXT:0000412	denotes	restriction fragment
T10301	15662-15663	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10302	15664-15665	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10303	15666-15670	NCBITaxon:10088	denotes	mice
T10304	15679-15680	CHEBI_SO_EXT:base	denotes	b
T10305	15698-15699	SO_EXT:sequence_nullness_or_absence	denotes	-
T10306	15700-15701	SO_EXT:sequence_nullness_or_absence	denotes	-
T10307	15702-15706	NCBITaxon:10088	denotes	mice
T10308	15742-15743	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10309	15744-15745	SO_EXT:sequence_nullness_or_absence	denotes	-
T10310	15746-15750	NCBITaxon:10088	denotes	mice
T10311	15762-15766	NCBITaxon:10088	denotes	Mice
T10312	15786-15788	PR_EXT:000006300	denotes	E2
T10313	15789-15797	SO_EXT:sequence_alteration_entity_or_process	denotes	mutation
T10314	15803-15807	GO:0007567	denotes	born
T10315	15835-15843	SO_EXT:genotype_or_entity_with_genotype	denotes	Genotype
T10316	15856-15860	NCBITaxon_UBERON_EXT:pup	denotes	pups
T10317	15874-15875	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10318	15876-15877	SO_EXT:sequence_nullness_or_absence	denotes	-
T10319	15881-15882	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10320	15883-15884	SO_EXT:sequence_nullness_or_absence	denotes	-
T10321	15885-15892	GO:0007618	denotes	matings
T10322	15907-15908	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10323	15909-15910	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10324	15912-15913	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10325	15914-15915	SO_EXT:sequence_nullness_or_absence	denotes	-
T10326	15921-15922	SO_EXT:sequence_nullness_or_absence	denotes	-
T10327	15923-15924	SO_EXT:sequence_nullness_or_absence	denotes	-
T10328	15925-15929	NCBITaxon:10088	denotes	mice
T10329	16001-16008	NCBITaxon:33208	denotes	animals
T10330	16034-16035	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10331	16036-16037	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10332	16053-16054	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10333	16055-16056	SO_EXT:sequence_nullness_or_absence	denotes	-
T10334	16076-16077	SO_EXT:sequence_nullness_or_absence	denotes	-
T10335	16078-16079	SO_EXT:sequence_nullness_or_absence	denotes	-
T10336	16091-16093	PR_EXT:000006300	denotes	E2
T10357	16576-16577	SO_EXT:sequence_nullness_or_absence	denotes	-
T10358	16578-16579	SO_EXT:sequence_nullness_or_absence	denotes	-
T10359	16580-16584	NCBITaxon_UBERON_EXT:pup	denotes	pups
T10360	16585-16589	GO:0016265	denotes	died
T10361	16609-16614	GO:0007567	denotes	birth
T10362	16642-16643	SO_EXT:sequence_nullness_or_absence	denotes	-
T10363	16644-16645	SO_EXT:sequence_nullness_or_absence	denotes	-
T10364	16646-16649	NCBITaxon_UBERON_EXT:pup	denotes	pup
T10365	16671-16676	GO:0007567	denotes	natal
T10366	16731-16734	NCBITaxon_UBERON_EXT:pup	denotes	pup
T12078	16748-16750	PR_EXT:000006300	denotes	E2
T12079	16761-16765	NCBITaxon:10088	denotes	mice
T12080	16820-16824	SO_EXT:0000704	denotes	gene
T12081	16856-16858	PR_EXT:000006300	denotes	E2
T12082	16859-16863	SO_EXT:sequence_nullness	denotes	null
T12083	16864-16870	SO_EXT:0001023	denotes	allele
T12084	16904-16909	UBERON:0002107	denotes	liver
T12085	16929-16934	GO:0007567	denotes	natal
T12086	16941-16946	NCBITaxon:10088	denotes	mouse
T12087	16947-16951	NCBITaxon_UBERON_EXT:pup	denotes	pups
T12088	16965-16966	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12089	16967-16968	SO_EXT:sequence_nullness_or_absence	denotes	-
T12090	16972-16973	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12091	16974-16975	SO_EXT:sequence_nullness_or_absence	denotes	-
T12092	16976-16982	GO:0007618	denotes	mating
T12093	17035-17036	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12094	17037-17038	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12095	17039-17043	NCBITaxon:10088	denotes	mice
T12096	17128-17129	SO_EXT:sequence_nullness_or_absence	denotes	-
T12097	17130-17131	SO_EXT:sequence_nullness_or_absence	denotes	-
T12098	17132-17137	NCBITaxon:10088	denotes	mouse
T12099	17138-17144	UBERON:0002107	denotes	livers
T12100	17176-17177	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12101	17178-17179	SO_EXT:sequence_nullness_or_absence	denotes	-
T12102	17180-17184	NCBITaxon:10088	denotes	mice
T12103	17230-17231	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12104	17232-17233	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12105	17276-17277	SO_EXT:sequence_nullness_or_absence	denotes	-
T12106	17278-17279	SO_EXT:sequence_nullness_or_absence	denotes	-
T12107	17280-17284	NCBITaxon:10088	denotes	mice
T12108	17317-17323	NCBITaxon:9606	denotes	humans
T12148	18926-18935	GO:0006537	denotes	glutamate
T12149	18941-18950	GO:0006542	denotes	glutamine
T12150	18917-18924	CHEBI_SO_EXT:alanine	denotes	alanine
T12151	18926-18935	CHEBI_EXT:glutamate	denotes	glutamate
T12152	18941-18950	CHEBI_SO_EXT:glutamine	denotes	glutamine
T12153	18977-18995	GO:0009081	denotes	metabolism of BCAA
T12154	18991-18995	CHEBI:22918	denotes	BCAA
T12155	19004-19008	NCBITaxon:10088	denotes	mice
T12156	19095-19100	UBERON:0000178	denotes	blood
T12157	19115-19122	CHEBI_SO_EXT:alanine	denotes	alanine
T12158	19124-19133	CHEBI_EXT:glutamate	denotes	glutamate
T12159	19139-19148	CHEBI_SO_EXT:glutamine	denotes	glutamine
T12160	19195-19206	CHEBI_SO_EXT:amino_acid	denotes	amino acids
T12161	19221-19225	NCBITaxon:10088	denotes	mice
T12162	19265-19266	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12163	19267-19268	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12164	19272-19273	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12165	19274-19275	SO_EXT:sequence_nullness_or_absence	denotes	-
T12166	19276-19280	NCBITaxon:10088	denotes	mice
T12167	19302-19313	CHEBI_SO_EXT:amino_acid	denotes	amino acids
T12168	19321-19322	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12169	19323-19324	SO_EXT:sequence_nullness_or_absence	denotes	-
T12170	19325-19329	NCBITaxon:10088	denotes	mice
T12171	19358-19359	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12172	19360-19361	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12173	19362-19366	NCBITaxon:10088	denotes	mice
T12174	19418-19423	UBERON:0000178	denotes	blood
T12175	19424-19431	CHEBI_SO_EXT:alanine	denotes	alanine
T12176	19457-19462	UBERON:0000178	denotes	blood
T12177	19463-19467	CHEBI:22918	denotes	BCAA
T12178	19573-19577	CHEBI:22918	denotes	BCAA
T12179	19578-19585	CHEBI_SO_EXT:alanine	denotes	alanine
T12180	19662-19666	CHEBI:22918	denotes	BCAA
T12181	19717-19727	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T12182	19739-19743	CHEBI:22918	denotes	BCAA
T12183	19744-19751	CHEBI_SO_EXT:alanine	denotes	alanine
T12184	19796-19797	SO_EXT:sequence_nullness_or_absence	denotes	-
T12185	19798-19799	SO_EXT:sequence_nullness_or_absence	denotes	-
T12186	19800-19804	NCBITaxon_UBERON_EXT:pup	denotes	pups
T12187	19838-19839	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12188	19840-19841	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12189	19845-19846	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12190	19847-19848	SO_EXT:sequence_nullness_or_absence	denotes	-
T12191	19868-19873	UBERON:0000178	denotes	blood
T12192	19874-19884	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T15719	29811-29815	CHEBI:22918	denotes	BCAA
T21290	37704-37713	GO:0008152	denotes	metabolic
T21289	37658-37666	CL_GO_EXT:cell	denotes	cellular
T21288	37649-37653	SO_EXT:0000704	denotes	gene
T21287	37505-37512	NCBITaxon:33208	denotes	animals
T21286	37445-37450	NCBITaxon:10088	denotes	mouse
T21285	37422-37433	SO_EXT:0000704	denotes	genetically
T21984	6693-6695	PR_EXT:000006300	denotes	E2
T21985	6696-6700	SO_EXT:0000704	denotes	gene
T21986	6710-6715	NCBITaxon:10088	denotes	mouse
T21987	6731-6735	SO_EXT:0000704	denotes	Gene
T21988	6778-6780	PR_EXT:000006300	denotes	E2
T21989	6790-6795	NCBITaxon:10088	denotes	mouse
T21990	6796-6804	CL:0002322	denotes	ES cells
T21991	6799-6804	CL_GO_EXT:cell	denotes	cells
T21992	6820-6829	SO_EXT:engineered_biological_sequence	denotes	construct
T21993	6846-6852	SO_EXT:sequence_deletion_process	denotes	delete
T21994	6859-6860	CHEBI_SO_EXT:base	denotes	b
T21995	6864-6872	SO_EXT:biological_sequence	denotes	sequence
T21996	6890-6902	SO_EXT:0000852	denotes	site in Exon
T21997	6924-6930	SO_EXT:0000188	denotes	intron
T21998	6938-6947	SO_EXT:wild_type_entity_or_quality	denotes	wild type
T21999	6948-6950	PR_EXT:000006300	denotes	E2
T22000	6951-6955	SO_EXT:0000704	denotes	gene
T22001	6973-6974	CHEBI_SO_EXT:base	denotes	b
T22002	6980-7000	SO_EXT:0000412	denotes	restriction fragment
T22003	7006-7016	GO:0097617	denotes	hybridizes
T22004	7024-7028	SO_EXT:0000147	denotes	Exon
T22005	7040-7045	CHEBI_SO_EXT:molecular_probe	denotes	probe
T22006	7068-7070	PR_EXT:000006300	denotes	E2
T22007	7093-7094	CHEBI_SO_EXT:base	denotes	b
T22008	7100-7120	SO_EXT:0000412	denotes	restriction fragment
T22009	7126-7136	GO:0097617	denotes	hybridizes
T22010	7149-7154	CHEBI_SO_EXT:molecular_probe	denotes	probe
T22011	7170-7175	CHEBI_SO_EXT:molecular_probe	denotes	probe
T22012	7218-7234	SO_EXT:0001644	denotes	targeting vector
T22013	7265-7281	SO_EXT:0001644	denotes	targeting vector
T22014	7326-7337	SO_EXT:genomic_DNA	denotes	genomic DNA
T22015	7334-7337	CHEBI_SO_EXT:DNA	denotes	DNA
T22016	7364-7373	SO_EXT:wild_type_entity_or_quality	denotes	wild type
T22017	7374-7381	CL:0002322	denotes	ES cell
T22018	7377-7381	CL_GO_EXT:cell	denotes	cell
T22019	7417-7424	CL:0002322	denotes	ES cell
T22020	7420-7424	CL_GO_EXT:cell	denotes	cell
T22021	7446-7455	SO_EXT:wild_type_entity_or_quality	denotes	wild type
T22022	7457-7458	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22023	7459-7460	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22024	7477-7478	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22025	7479-7480	SO_EXT:sequence_nullness_or_absence	denotes	-
T22026	7507-7508	SO_EXT:sequence_nullness_or_absence	denotes	-
T22027	7509-7510	SO_EXT:sequence_nullness_or_absence	denotes	-
T22028	7512-7516	NCBITaxon:10088	denotes	mice
T22029	7531-7541	GO:0097617	denotes	hybridized
T22030	7550-7554	SO_EXT:0000147	denotes	Exon
T22031	7566-7571	CHEBI_SO_EXT:molecular_probe	denotes	probe
T22032	7621-7626	UBERON:0002107	denotes	liver
T22033	7650-7651	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22034	7652-7653	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22035	7659-7661	PR_EXT:000006300	denotes	E2
T22036	7672-7673	SO_EXT:sequence_nullness_or_absence	denotes	-
T22037	7674-7675	SO_EXT:sequence_nullness_or_absence	denotes	-
T22038	7681-7686	GO:0007567	denotes	natal
T22039	7693-7698	NCBITaxon:10088	denotes	mouse
T22040	7699-7703	NCBITaxon_UBERON_EXT:pup	denotes	pups
T22041	7731-7733	PR_EXT:000006300	denotes	E2
T22042	7743-7745	PR_EXT:000006300	denotes	E2
T22043	7755-7763	GO:0042571	denotes	antibody
T22044	7778-7785	GO:0005634	denotes	nuclear
T22045	7829-7831	PR_EXT:000006300	denotes	E2
T22046	7882-7887	NCBITaxon:10088	denotes	mouse
T22047	7967-7972	NCBITaxon:10088	denotes	mouse
T22048	7973-7982	UBERON:0000922	denotes	embryonic
T22049	7983-7994	CL:0000057	denotes	fibroblasts
T22050	8047-8049	PR_EXT:000006300	denotes	E2
T22051	8065-8070	CL_GO_EXT:cell	denotes	cells
T22052	8114-8126	GO:0005739	denotes	mitochondria
T22053	8132-8143	GO_UBERON_EXT:cellular_component_or_cell_part	denotes	subcellular
T22054	8135-8143	CL_GO_EXT:cell	denotes	cellular
T22750	17357-17368	CHEBI_EXT:biochemical	denotes	Biochemical
T22751	17406-17412	NCBITaxon:39107	denotes	murine
T22752	17429-17435	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T22753	17448-17453	UBERON:0002107	denotes	liver
T22754	17457-17464	PATO_UBERON_EXT:neonate_or_newborn	denotes	newborn
T22755	17465-17474	SO_EXT:wild_type_entity_or_quality	denotes	wild type
T22756	17484-17485	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22757	17486-17487	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22758	17504-17505	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22759	17506-17507	SO_EXT:sequence_nullness_or_absence	denotes	-
T22760	17526-17527	SO_EXT:sequence_nullness_or_absence	denotes	-
T22761	17528-17529	SO_EXT:sequence_nullness_or_absence	denotes	-
T22762	17540-17544	NCBITaxon:10088	denotes	mice
T22763	17546-17552	CHEBI_GO_SO_EXT:enzyme	denotes	Enzyme
T22764	17591-17592	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22765	17593-17594	SO_EXT:sequence_nullness_or_absence	denotes	-
T22766	17595-17600	UBERON:0002107	denotes	liver
T22767	17613-17614	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22768	17615-17616	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22769	17658-17659	SO_EXT:sequence_nullness_or_absence	denotes	-
T22770	17660-17661	SO_EXT:sequence_nullness_or_absence	denotes	-
T22771	17662-17667	UBERON:0002107	denotes	liver
T22772	17678-17682	CHEBI:22918	denotes	BCAA
T22773	17701-17706	UBERON:0000178	denotes	blood
T22774	17710-17714	NCBITaxon:10088	denotes	mice
T22775	17722-17726	CHEBI:22918	denotes	BCAA
T22776	17748-17755	CHEBI_SO_EXT:leucine	denotes	leucine
T22777	17757-17767	CHEBI_SO_EXT:isoleucine	denotes	isoleucine
T22778	17773-17779	CHEBI_SO_EXT:valine	denotes	valine
T22779	17787-17791	CHEBI:22918	denotes	BCAA
T22780	17810-17815	UBERON:0000178	denotes	blood
T22781	17821-17822	SO_EXT:sequence_nullness_or_absence	denotes	-
T22782	17823-17824	SO_EXT:sequence_nullness_or_absence	denotes	-
T22783	17825-17829	NCBITaxon:10088	denotes	mice
T22784	17870-17871	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22785	17872-17873	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22786	17878-17879	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22787	17880-17881	SO_EXT:sequence_nullness_or_absence	denotes	-
T22788	17901-17905	CHEBI:22918	denotes	BCAA
T22789	17909-17916	CHEBI_SO_EXT:alanine	denotes	alanine
T22790	17920-17925	UBERON:0000178	denotes	blood
T22791	17929-17933	NCBITaxon:10088	denotes	mice
T22792	17976-17977	SO_EXT:sequence_nullness_or_absence	denotes	-
T22793	17978-17979	SO_EXT:sequence_nullness_or_absence	denotes	-
T22794	17980-17984	NCBITaxon:10088	denotes	mice
T22795	17997-17998	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22796	17999-18000	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22797	18005-18006	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22798	18007-18008	SO_EXT:sequence_nullness_or_absence	denotes	-
T22799	18009-18013	NCBITaxon:10088	denotes	mice
T22800	18063-18067	NCBITaxon:10088	denotes	mice
T22801	18110-18111	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22802	18112-18113	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22803	18160-18161	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22804	18162-18163	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22805	18168-18169	SO_EXT:normal_or_wild_type_or_present	denotes	+
T22806	18170-18171	SO_EXT:sequence_nullness_or_absence	denotes	-
T24771	20000-20005	UBERON:0000178	denotes	blood
T24772	20006-20016	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T24773	20158-20163	GO:0007567	denotes	birth
T10340	16193-16197	NCBITaxon:10088	denotes	mice
T10341	16198-16202	GO:0016265	denotes	died
T10342	16210-16226	UBERON:0012101	denotes	perinatal period
T10343	16214-16219	GO:0007567	denotes	natal
T10344	16250-16255	GO:0007567	denotes	birth
T12130	18547-18552	UBERON:0000178	denotes	blood
T12131	18569-18574	UBERON:0001088	denotes	urine
T12132	18602-18606	CHEBI:22918	denotes	BCAA
T10337	16094-16098	SO_EXT:0000704	denotes	gene
T10338	16126-16135	UBERON:0000922	denotes	embryonic
T10339	16126-16147	GO:0009790	denotes	embryonic development
T10345	16268-16272	NCBITaxon_UBERON_EXT:pup	denotes	pups
T10346	16307-16308	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10347	16309-16310	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10348	16315-16316	SO_EXT:normal_or_wild_type_or_present	denotes	+
T10349	16317-16318	SO_EXT:sequence_nullness_or_absence	denotes	-
T10350	16371-16377	GO:0001967	denotes	suckle
T10351	16405-16410	GO:0007567	denotes	natal
T10352	16425-16426	SO_EXT:sequence_nullness_or_absence	denotes	-
T10353	16427-16428	SO_EXT:sequence_nullness_or_absence	denotes	-
T10354	16429-16433	NCBITaxon_UBERON_EXT:pup	denotes	pups
T10355	16532-16543	UBERON:0001004	denotes	respiratory
T10356	16544-16553	GO_EXT:biological_movement_or_translocation_process	denotes	movements
T12109	18214-18216	PR_EXT:000006300	denotes	E2
T12110	18226-18234	GO:0042571	denotes	antibody
T12111	18255-18257	PR_EXT:000006300	denotes	E2
T12112	18258-18265	CHEBI_PR_EXT:protein	denotes	protein
T12113	18273-18277	NCBITaxon:10088	denotes	mice
T12114	18324-18326	PR_EXT:000006300	denotes	E2
T12115	18327-18334	CHEBI_PR_EXT:protein	denotes	protein
T12116	18351-18356	UBERON:0002107	denotes	liver
T12117	18361-18370	UBERON:0000922	denotes	embryonic
T12118	18371-18382	CL:0000057	denotes	fibroblasts
T12119	18385-18386	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12120	18387-18388	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12121	18389-18393	NCBITaxon:10088	denotes	mice
T12122	18430-18432	PR_EXT:000006300	denotes	E2
T12123	18433-18440	CHEBI_PR_EXT:protein	denotes	protein
T12124	18466-18473	UBERON:0000479	denotes	tissues
T12125	18477-18478	SO_EXT:sequence_nullness_or_absence	denotes	-
T12126	18479-18480	SO_EXT:sequence_nullness_or_absence	denotes	-
T12127	18481-18485	NCBITaxon:10088	denotes	mice
T12128	18498-18500	PR_EXT:000006300	denotes	E2
T12129	18510-18514	NCBITaxon:10088	denotes	mice
T12133	18615-18622	CHEBI_SO_EXT:leucine	denotes	leucine
T12134	18624-18634	CHEBI_SO_EXT:isoleucine	denotes	isoleucine
T12135	18640-18646	CHEBI_SO_EXT:valine	denotes	valine
T12136	18669-18670	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12137	18671-18672	SO_EXT:normal_or_wild_type_or_present	denotes	+
T12138	18694-18705	CHEBI_SO_EXT:amino_acid	denotes	amino acids
T12139	18760-18764	CHEBI:22918	denotes	BCAA
T12140	18801-18815	CHEBI_EXT:alloisoleucine	denotes	alloisoleucine
T12141	18847-18848	SO_EXT:sequence_nullness_or_absence	denotes	-
T12142	18849-18850	SO_EXT:sequence_nullness_or_absence	denotes	-
T12143	18856-18860	NCBITaxon:10088	denotes	mice
T12144	18866-18884	GO:0009081	denotes	metabolism of BCAA
T12145	18880-18884	CHEBI:22918	denotes	BCAA
T12146	18904-18924	GO:0006523	denotes	synthesis of alanine
T12147	18904-18916	_FRAGMENT	denotes	synthesis of
T3181	11-16	NCBITaxon:4022	denotes	Maple
T3182	23-28	UBERON:0001088	denotes	Urine
T3183	49-56	SO_EXT:0000704	denotes	genetic
T3184	107-116	CHEBI:25754	denotes	keto acid
T3185	142-155	GO:0005739	denotes	mitochondrial
T3186	161-167	CHEBI_GO_SO_EXT:enzyme	denotes	enzyme
T3187	168-175	GO:0032991	denotes	complex
T3188	196-205	MOP:0000568	denotes	oxidative
T15512	21228-21230	PR_EXT:000006300	denotes	E2
T15511	21222-21227	NCBITaxon:9606	denotes	human
T15510	21214-21221	GO:0010467	denotes	express
T15509	21193-21203	SO_EXT:transgenic_entity	denotes	transgenic
T15508	21140-21145	NCBITaxon:10088	denotes	mouse
T15507	21098-21107	GO_EXT:fatality_or_lethality	denotes	lethality
T15506	21089-21097	PATO_UBERON_EXT:neonate_or_newborn	denotes	neonatal
T15505	21080-21084	CHEBI:22918	denotes	BCAA
T15504	21049-21055	SO_EXT:sequence_rescue_process	denotes	rescue
T15503	21026-21036	SO_EXT:transgenic_entity	denotes	transgenic
T15502	20961-20967	NCBITaxon:39107	denotes	murine
T15501	20880-20889	SO_EXT:0000902	denotes	transgene
T15500	20877-20879	PR_EXT:000006300	denotes	E2
T15499	20871-20876	NCBITaxon:9606	denotes	human
T15498	20858-20868	GO:0010467	denotes	expressing
T15497	20853-20857	NCBITaxon:10088	denotes	mice
T3291	4729-4738	UBERON:0000922	denotes	embryonic
T3292	4729-4743	_FRAGMENT	denotes	embryonic stem
T3293	4749-4754	CL:0002322	denotes	cells
T3294	4745-4747	_FRAGMENT	denotes	ES
T3295	4749-4754	CL_GO_EXT:cell	denotes	cells
T3296	4810-4820	SO_EXT:transgenic_entity	denotes	transgenic
T3297	4821-4827	SO_EXT:sequence_rescue_process	denotes	rescue
T3298	4835-4837	PR_EXT:000006300	denotes	E2
T3299	4838-4842	SO_EXT:0000704	denotes	gene
T3300	4920-4926	NCBITaxon:39107	denotes	murine
T3301	5026-5030	SO_EXT:0000704	denotes	gene
T3302	5034-5043	CL:0000034	denotes	stem cell
T3303	5039-5043	CL_GO_EXT:cell	denotes	cell
T15565	23802-23806	SO_EXT:sequence_copy_entity	denotes	copy
T15564	23792-23801	SO_EXT:0000902	denotes	transgene
T15563	23641-23651	SO_EXT:transgenic_entity	denotes	transgenic
T15562	23569-23584	SO_EXT:0000366	denotes	insertion sites
T15561	23559-23568	SO_EXT:0000902	denotes	transgene
T15560	23538-23545	NCBITaxon:33208	denotes	animals
T15559	23485-23493	GO_EXT:breeding	denotes	breeding
T15558	23445-23454	SO_EXT:0000902	denotes	transgene
T15557	23342-23352	SO_EXT:transgenic_entity	denotes	transgenic
T15556	23256-23265	SO_EXT:0000902	denotes	transgene
T15555	23194-23203	SO_EXT:0000902	denotes	transgene
T15554	23191-23193	PR_EXT:000006300	denotes	E2
T15553	23164-23168	NCBITaxon:10088	denotes	mice
T15552	23153-23163	SO_EXT:transgenic_entity	denotes	transgenic
T15551	23107-23117	GO:0045120	denotes	Pronuclear
T15550	23071-23072	NCBITaxon:10088	denotes	i
T15549	23065-23066	CHEBI_PR_EXT:protein	denotes	r
T15548	23062-23063	UBERON_EXT:muscle_structure_or_tissue	denotes	c
T15547	23056-23057	UBERON:0002113	denotes	d
T15546	23055-23056	NCBITaxon:10088	denotes	e
T15545	23054-23055	SO_EXT:transgenic_entity	denotes	c
T15544	23053-23054	NCBITaxon:9606	denotes	u
T15543	23052-23053	GO:0042571	denotes	d
T15542	23041-23042	UBERON:0002107	denotes	v
T15541	23038-23041	CHEBI_PR_EXT:protein	denotes	pre
T15624	26496-26503	CHEBI_SO_EXT:alanine	denotes	alanine
T15623	26491-26495	CHEBI:22918	denotes	BCAA
T15622	26478-26485	CHEBI_SO_EXT:alanine	denotes	alanine
T15621	26470-26474	CHEBI:22918	denotes	BCAA
T15620	26420-26430	CHEBI_SO_EXT:amino_acid	denotes	amino acid
T15619	26414-26419	UBERON:0000178	denotes	blood
T15618	26367-26368	GO_EXT:killing	denotes	c
T15617	26333-26334	UBERON:0000178	denotes	d
T15616	26331-26333	CHEBI_SO_EXT:alanine	denotes	an
T15615	26329-26330	CHEBI:22918	denotes	A
T15614	26326-26327	SO_EXT:genotype_or_entity_with_genotype	denotes	e
T15613	26323-26324	PR_EXT:000005308	denotes	L
T15612	25149-25153	NCBITaxon_UBERON_EXT:pup	denotes	pups
T15611	25099-25106	NCBITaxon:33208	denotes	animals
T15610	25092-25098	SO_EXT:sequence_rescue_process	denotes	rescue
T15609	25032-25038	GO_EXT:fatality_or_lethality	denotes	lethal
T15608	25023-25031	PATO_UBERON_EXT:neonate_or_newborn	denotes	neonatal
T15607	25012-25018	SO_EXT:sequence_rescue_process	denotes	rescue
T15606	24955-24957	PR_EXT:000006300	denotes	E2
T15605	24931-24937	GO_EXT:fatality_or_lethality	denotes	lethal
T15604	24922-24930	PATO_UBERON_EXT:neonate_or_newborn	denotes	neonatal
T15603	24909-24917	SO_EXT:sequence_rescue_process	denotes	rescuing
T15602	24865-24874	SO_EXT:0000902	denotes	transgene
T15601	24840-24848	SO_EXT:genotype_or_entity_with_genotype	denotes	genotype
T15600	24833-24839	SO_EXT:sequence_rescue_process	denotes	rescue
R2280	T8086	T8085	_lexicallyChainedTo	isocaproate,α-keto
R343	T3217	T3216	_lexicallyChainedTo	subunits,α
R344	T3223	T3222	_lexicallyChainedTo	dehydrogenase,pyruvate
R345	T3224	T3222	_lexicallyChainedTo	dehydrogenase complexes,pyruvate
R346	T3293	T3292	_lexicallyChainedTo	cells,embryonic stem
R347	T3293	T3294	_lexicallyChainedTo	cells,ES
R2281	T8098	T8097	_lexicallyChainedTo	isocaproate,α-keto
R3288	T12148	T12147	_lexicallyChainedTo	glutamate,synthesis of
R3289	T12149	T12147	_lexicallyChainedTo	glutamine,synthesis of
R3834	T15647	T15646	_lexicallyChainedTo	protein,production of

craft-ca-core-dev

Below, discontinuous spans are shown in the chain model. You can change it to the bag model.

Id	Subject	Object	Predicate	Lexical cue
T24910	27073-27077	NCBITaxon:10088	denotes	mice
T24909	26923-26928	UBERON:0000178	denotes	blood
T24414	26198-26202	NCBITaxon:10088	denotes	mice
T24413	26163-26167	NCBITaxon:10088	denotes	mice
T24412	26104-26108	NCBITaxon:10088	denotes	mice
T24411	26066-26071	UBERON:0002107	denotes	liver
T24410	25834-25838	CHEBI:22918	denotes	BCAA
T24409	25775-25779	CHEBI:22918	denotes	BCAA
T24408	25728-25732	NCBITaxon:10088	denotes	mice
T24407	25719-25724	UBERON:0000178	denotes	blood
T24406	25700-25704	CHEBI:22918	denotes	BCAA
T24405	25596-25603	NCBITaxon:33208	denotes	animals
T24404	25476-25486	SO:0000902	denotes	transgenes
T24403	25473-25475	PR:000006300	denotes	E2
T24402	25457-25460	PR:000005308	denotes	LAP
T24401	25428-25430	PR:000006300	denotes	E2
T24400	25299-25303	NCBITaxon:10088	denotes	mice
T24399	25207-25213	NCBITaxon:10088	denotes	murine
T23587	22948-22956	GO:0042571	denotes	antibody
T23586	22942-22947	PR:000003676	denotes	actin
T23585	22900-22907	UBERON:0000479	denotes	tissues
T23584	22888-22890	PR:000006300	denotes	E2
T23583	22870-22879	SO:0000902	denotes	transgene
T23582	22812-22818	UBERON:0002113	denotes	kidney
T23581	22801-22806	UBERON:0000955	denotes	brain
T23580	22750-22754	NCBITaxon:10088	denotes	mice
T23579	22733-22735	PR:000006300	denotes	E2
T23578	22727-22732	NCBITaxon:9606	denotes	human
T23577	22713-22718	PR:000000084	denotes	c-myc
T23576	22694-22703	SO:0000902	denotes	transgene
T23575	22655-22663	GO:0042571	denotes	antibody
T23574	22645-22650	PR:000000084	denotes	c-myc
T23573	22618-22625	NCBITaxon:33208	denotes	animals
T23572	22592-22594	PR:000006300	denotes	E2
T19647	36885-36890	UBERON:0000178	denotes	blood
T19646	36842-36849	CHEBI:26948	denotes	thiamin
T19645	36797-36802	NCBITaxon:10088	denotes	mouse
T19644	36725-36731	SO:0001023	denotes	allele
T19643	36714-36724	GO:0010467	denotes	expressing
T19642	36711-36713	PR:000006300	denotes	E2
T19641	36635-36642	CHEBI:26948	denotes	thiamin
T19640	36519-36526	CHEBI:26948	denotes	thiamin
T19639	36379-36386	CHEBI:26948	denotes	thiamin
T19638	36368-36375	CHEBI:26948	denotes	thiamin
T19637	36265-36271	UBERON:0000479	denotes	tissue
T19636	36190-36195	NCBITaxon:9606	denotes	human
T19635	35968-35974	NCBITaxon:9606	denotes	humans
T19634	35864-35870	NCBITaxon:33208	denotes	animal
T19633	35723-35729	NCBITaxon:33208	denotes	animal
T19632	35678-35682	SO:0000704	denotes	gene
T19631	35621-35628	SO:0000704	denotes	genetic
T19630	35604-35610	NCBITaxon:33208	denotes	animal
T19629	35551-35557	NCBITaxon:9606	denotes	humans
T19628	35535-35539	SO:0000704	denotes	gene
T19627	35500-35504	SO:0000704	denotes	gene
T19626	35460-35480	CL:0002322	denotes	embryonic stem cells
T19625	35460-35469	UBERON:0000922	denotes	embryonic
T19624	35437-35448	CL:0000182	denotes	hepatocytes
T19623	35392-35396	SO:0000704	denotes	gene
T19622	35343-35348	NCBITaxon:10088	denotes	mouse
T19621	35276-35281	NCBITaxon:9606	denotes	human
T19620	35193-35199	NCBITaxon:39107	denotes	murine
T19619	35125-35131	NCBITaxon:9606	denotes	humans
T19618	35106-35109	NCBITaxon:9913	denotes	cow
T19617	35034-35040	NCBITaxon:33208	denotes	animal
T19616	34910-34913	NCBITaxon:9913	denotes	cow
T19615	34895-34900	NCBITaxon:10088	denotes	mouse
T19614	34606-34610	CHEBI:22918	denotes	BCAA
T19613	34600-34605	UBERON:0000178	denotes	blood
T19612	34567-34572	NCBITaxon:10088	denotes	mouse
T19611	34542-34547	UBERON:0002107	denotes	liver
T19610	34505-34509	SO:0000704	denotes	gene
T19609	34486-34504	PR:000004683	denotes	mitochondrial BCAT
T19608	34486-34499	GO:0005739	denotes	mitochondrial
T19607	34434-34439	NCBITaxon:9606	denotes	human
T19606	34417-34422	NCBITaxon:10088	denotes	mouse
T19605	34413-34416	CHEBI:23995	denotes	ENU
T19604	34295-34304	GO:0065007	denotes	regulated
T19603	34185-34195	GO:0010467	denotes	expression
T19602	34175-34184	GO:0065007	denotes	regulated
T19601	34141-34151	SO:0000902	denotes	transgenes
T19600	34117-34133	SO:0000366	denotes	integration site
T19599	34066-34077	CHEBI:50845	denotes	doxycycline
T19598	33943-33954	CHEBI:50845	denotes	doxycycline
T19597	33920-33932	CHEBI:27902	denotes	tetracycline
T19596	33897-33905	SO:0005853	denotes	cassette
T19595	33886-33896	GO:0010467	denotes	expression
T19594	33883-33885	PR:000006300	denotes	E2
T19593	33877-33882	NCBITaxon:9606	denotes	human
T19592	33813-33822	SO:0000902	denotes	transgene
T19591	33662-33666	NCBITaxon:10088	denotes	mice
T19590	33522-33526	SO:0000704	denotes	gene
T19589	33512-33521	GO:0065007	denotes	regulated
T19588	33499-33511	CHEBI:27902	denotes	tetracycline
T19587	33359-33365	NCBITaxon:33208	denotes	animal
T19586	33329-33333	NCBITaxon:10088	denotes	mice
T19585	33306-33317	SO:0000704	denotes	genetically
T19584	33284-33289	NCBITaxon:9606	denotes	human
T19583	33272-33276	NCBITaxon:10088	denotes	mice
T19582	33158-33162	CHEBI:22918	denotes	BCAA
T19581	33106-33111	NCBITaxon:9606	denotes	human
T19580	33016-33020	NCBITaxon:10088	denotes	mice
T19579	32994-32999	UBERON:0000178	denotes	blood
T19543	31247-31249	PR:000006300	denotes	E2
T19542	31226-31230	CHEBI:22918	denotes	BCAA
T19541	31214-31225	GO:0008152	denotes	metabolized
T19540	31148-31153	NCBITaxon:10088	denotes	mouse
T19539	31118-31124	UBERON:0002107	denotes	livers
T19538	31061-31065	CHEBI:22918	denotes	BCAA
T19537	31047-31065	GO:0009081	denotes	metabolism of BCAA
T19536	30904-30908	CHEBI:22918	denotes	BCAA
T19535	30888-30893	UBERON:0000178	denotes	blood
T19534	30878-30886	GO:0001967	denotes	suckling
T19533	30858-30863	GO:0007567	denotes	birth
T19532	30835-30840	GO:0007567	denotes	birth
T19531	30781-30785	GO:0007567	denotes	born
T19530	30771-30775	NCBITaxon:10088	denotes	mice
T19529	30736-30742	NCBITaxon:9606	denotes	humans
T19528	30703-30710	NCBITaxon:33208	denotes	animals
T19527	30650-30669	PR:000006300	denotes	E2 subunit of BCKDH
T19526	30629-30633	SO:0000704	denotes	gene
T19525	30465-30470	NCBITaxon:10088	denotes	mouse
T19524	30442-30453	SO:0000704	denotes	genetically
T19523	30306-30312	NCBITaxon:33208	denotes	animal
T19650	37272-37285	GO:0005739	denotes	mitochondrial
T19649	37008-37017	GO:0032991	denotes	complexes
T19648	36935-36941	NCBITaxon:33208	denotes	animal
T15496	30127-30131	NCBITaxon:10088	denotes	mice
T15495	29949-29954	UBERON:0002107	denotes	liver
T15494	29894-29903	GO:0010467	denotes	expressed
T15493	29811-29815	CHEBI:22918	denotes	BCAA
T15492	29802-29806	NCBITaxon:10088	denotes	mice
T15491	29742-29746	GO:0016265	denotes	died
T15490	29684-29688	NCBITaxon:10088	denotes	mice
T15489	29514-29518	NCBITaxon:10088	denotes	mice
T15488	29475-29479	NCBITaxon:10088	denotes	mice
T15487	29397-29404	NCBITaxon:33208	denotes	animals
T15486	29273-29277	NCBITaxon:10088	denotes	mice
T15485	29238-29245	UBERON:0000479	denotes	tissues
T15484	29212-29214	PR:000006300	denotes	E2
T15483	29198-29208	GO:0010467	denotes	expression
T15473	28966-28977	PR:000006506	denotes	E3 subunits
T15472	28953-28958	NCBITaxon:10088	denotes	mouse
T15471	28938-28947	GO:0032991	denotes	complexed
T15470	28905-28907	PR:000006300	denotes	E2
T15469	28899-28904	NCBITaxon:9606	denotes	human
T15468	28851-28867	GO:0065003	denotes	subunit assembly
T15467	28812-28819	NCBITaxon:562	denotes	E. coli
T15466	28669-28699	GO:0045254	denotes	pyruvate dehydrogenase complex
T15465	28669-28677	CHEBI:15361	denotes	pyruvate
T15464	28497-28499	PR:000006300	denotes	E2
T15463	28491-28496	NCBITaxon:9606	denotes	human
T15462	28473-28482	SO:0000902	denotes	transgene
T15461	28432-28437	PR:000000084	denotes	c-myc
T15460	28367-28369	PR:000006300	denotes	E2
T15459	28349-28358	SO:0000902	denotes	transgene
T15458	28272-28274	PR:000006300	denotes	E2
T15457	28215-28219	NCBITaxon:10088	denotes	mice
T15456	28184-28189	UBERON:0002107	denotes	liver
T15455	28160-28162	PR:000006300	denotes	E2
T15454	28154-28159	NCBITaxon:10088	denotes	mouse
T15453	28110-28112	PR:000006300	denotes	E2
T15452	28104-28109	NCBITaxon:9606	denotes	human
T15451	28085-28089	NCBITaxon:10088	denotes	mice
T15450	28051-28055	NCBITaxon:10088	denotes	mice
T15449	28019-28023	NCBITaxon:10088	denotes	mice
T15448	27975-27977	PR:000006300	denotes	E2
T15447	27969-27974	NCBITaxon:9606	denotes	human
T15446	27917-27922	UBERON:0002107	denotes	liver
T15445	27815-27820	UBERON:0002107	denotes	liver
T15444	27747-27752	UBERON:0002107	denotes	liver
T15443	27733-27735	PR:000006300	denotes	E2
T15442	27727-27732	NCBITaxon:9606	denotes	human
T15441	27736-27743	GO:0006412	denotes	protein
T15440	27713-27726	_FRAGMENT	denotes	production of
T15439	27670-27680	GO:0010467	denotes	expression
T15438	27655-27660	UBERON:0002107	denotes	liver
T15437	27618-27620	PR:000006300	denotes	E2
T15436	27612-27617	NCBITaxon:9606	denotes	human
T15435	27587-27597	GO:0010467	denotes	expression
T15434	27558-27562	NCBITaxon:10088	denotes	mice
T15433	27550-27553	PR:000005308	denotes	LAP
T15432	26854-26858	NCBITaxon:10088	denotes	mice
T15380	21700-21708	SO:0000167	denotes	promoter
T15379	21662-21664	PR:000006300	denotes	E2
T15378	21656-21661	NCBITaxon:9606	denotes	human
T15377	21646-21653	GO:0010467	denotes	express
T15376	21620-21629	SO:0000902	denotes	transgene
T15375	21617-21619	PR:000006300	denotes	E2
T15374	21546-21555	SO:0000167	denotes	promoters
T15373	21532-21542	GO:0010467	denotes	expression
T15372	21460-21470	GO:0065007	denotes	controlled
T15371	21447-21459	CHEBI:27902	denotes	tetracycline
T15370	21429-21439	GO:0010467	denotes	expression
T15369	21414-21419	UBERON:0002107	denotes	liver
T15368	21376-21385	SO:0000902	denotes	transgene
T15367	21368-21371	PR:000005308	denotes	LAP
T15366	21343-21352	SO:0000902	denotes	transgene
T15365	21340-21342	PR:000006300	denotes	E2
T15364	21320-21329	SO:0000902	denotes	transgene
T15363	21312-21315	PR:000005308	denotes	LAP
T15362	21247-21249	PR:000006300	denotes	E2
T15361	21234-21239	UBERON:0002107	denotes	liver
T15360	21228-21230	PR:000006300	denotes	E2
T15359	21222-21227	NCBITaxon:9606	denotes	human
T15358	21214-21221	GO:0010467	denotes	express
T15357	21140-21145	NCBITaxon:10088	denotes	mouse
T15356	21080-21084	CHEBI:22918	denotes	BCAA
T15355	20961-20967	NCBITaxon:39107	denotes	murine
T15354	20880-20889	SO:0000902	denotes	transgene
T15353	20877-20879	PR:000006300	denotes	E2
T15352	20871-20876	NCBITaxon:9606	denotes	human
T15351	20858-20868	GO:0010467	denotes	expressing
T15350	20853-20857	NCBITaxon:10088	denotes	mice
T12076	20798-20800	PR:000006300	denotes	E2
T12075	20754-20760	NCBITaxon:9606	denotes	humans
T12074	20630-20639	GO:0008152	denotes	metabolic
T12073	20617-20622	UBERON:0001088	denotes	urine
T12072	20607-20612	UBERON:0000178	denotes	blood
T12071	20595-20599	CHEBI:22918	denotes	BCAA
T12070	20537-20539	PR:000006300	denotes	E2
T12069	20501-20505	NCBITaxon:10088	denotes	mice
T12068	20489-20491	PR:000006300	denotes	E2
T3120	1532-1534	PR:000006506	denotes	E3
T3123	1600-1610	PR:000004687	denotes	β subunits
T3124	1627-1629	PR:000006300	denotes	E2
T3125	1672-1674	PR:000006506	denotes	E3
T3126	1691-1699	CHEBI:15361	denotes	pyruvate
T3127	1691-1699	_FRAGMENT	denotes	pyruvate
T3128	1720-1743	GO:0045254	denotes	dehydrogenase complexes
T3129	1704-1743	GO:0045240	denotes	α-ketoglutarate dehydrogenase complexes
T3130	1756-1779	GO:0005960	denotes	glycine cleavage system
T3131	1764-1772	MOP:0000780	denotes	cleavage
T3132	1819-1829	GO:0065007	denotes	regulatory
T3133	1882-1890	GO:0065007	denotes	regulate
T3134	1964-1981	GO:0016311	denotes	dephosphorylation
T3135	2008-2020	PR:000004686	denotes	E1 α subunit
T3136	2045-2050	SO:0000704	denotes	genes
T3137	2065-2085	PR:000006300	denotes	E2 subunits of BCKDH
T3138	2178-2188	PR:000006300	denotes	E2 subunit
T3139	2264-2274	GO:0065007	denotes	regulatory
T3140	2401-2405	CHEBI:22918	denotes	BCAA
T3141	2516-2525	GO:0008152	denotes	metabolic
T3142	2780-2785	UBERON:0002107	denotes	liver
T3143	2789-2810	GO:0006520	denotes	amino acid metabolism
T3144	2857-2862	NCBITaxon:9606	denotes	human
T3145	2863-2868	UBERON:0002107	denotes	liver
T3146	2928-2933	UBERON:0002107	denotes	liver
T3147	2991-2996	UBERON:0002107	denotes	liver
T3148	3128-3145	CHEBI:35705	denotes	immunosuppressant
T3149	3146-3151	CHEBI:23888	denotes	drugs
T3150	3253-3258	UBERON:0002107	denotes	liver
T3151	3305-3311	UBERON:0002107	denotes	livers
T3152	3615-3621	NCBITaxon:33208	denotes	animal
T3153	3857-3863	NCBITaxon:33208	denotes	animal
T3154	3875-3880	NCBITaxon:9606	denotes	human
T3155	3962-3968	NCBITaxon:33208	denotes	animal
T3156	4000-4005	NCBITaxon:9606	denotes	human
T3157	4027-4048	CHEBI:23995	denotes	N-ethyl-N-nitrosourea
T3158	4050-4053	CHEBI:23995	denotes	ENU
T3159	4070-4075	NCBITaxon:10088	denotes	mouse
T3160	4106-4111	NCBITaxon:9606	denotes	human
T3161	4189-4195	GO:0008380	denotes	splice
T3162	4189-4200	SO:0000162	denotes	splice site
T3163	4208-4221	GO:0005739	denotes	mitochondrial
T3164	4208-4253	PR:000004683	denotes	mitochondrial branched-chain aminotransferase
T3165	4261-4265	SO:0000704	denotes	gene
T3166	4377-4382	NCBITaxon:10088	denotes	mouse
T3167	4401-4406	NCBITaxon:9606	denotes	human
T3168	4478-4489	SO:0000704	denotes	genetically
T3169	4501-4507	NCBITaxon:39107	denotes	murine
T3170	4601-4606	NCBITaxon:9606	denotes	human
T3171	4678-4697	PR:000006300	denotes	E2 subunit of BCKDH
T3172	4729-4738	UBERON:0000922	denotes	embryonic
T3173	4729-4743	_FRAGMENT	denotes	embryonic stem
T3174	4749-4754	CL:0002322	denotes	cells
T3175	4745-4747	_FRAGMENT	denotes	ES
T3176	4835-4837	PR:000006300	denotes	E2
T3177	4838-4842	SO:0000704	denotes	gene
T3178	4920-4926	NCBITaxon:39107	denotes	murine
T3179	5026-5030	SO:0000704	denotes	gene
T3180	5034-5043	CL:0000034	denotes	stem cell
T4355	5111-5118	NCBITaxon:33208	denotes	animals
T4356	5194-5200	NCBITaxon:33208	denotes	Animal
T4935	5226-5230	SO:0000704	denotes	Gene
T4936	5253-5260	SO:0001026	denotes	genomic
T4937	5313-5329	SO:0000852	denotes	portion of Exons
T4938	5345-5347	PR:000006300	denotes	E2
T4939	5348-5352	SO:0000704	denotes	gene
T4940	5357-5365	SO:0000357	denotes	flanking
T4941	5390-5398	NCBITaxon:10678	denotes	P1 phage
T4942	5412-5418	SO:0001026	denotes	Genome
T4943	5457-5462	NCBITaxon:10088	denotes	Mouse
T4944	5463-5465	CL:0002322	denotes	ES
T4945	5514-5518	SO:0000704	denotes	gene
T4946	5519-5535	SO:0001644	denotes	targeting vector
T4947	5612-5627	SO:0000852	denotes	portion of Exon
T4948	5641-5645	SO:0000147	denotes	Exon
T4949	5671-5675	SO:0000704	denotes	gene
T4950	5704-5710	SO:0000440	denotes	vector
T4951	5793-5801	CL:0002322	denotes	ES cells
T4952	5851-5859	CL:0002322	denotes	ES cells
T4953	5879-5883	CHEBI:42768	denotes	G418
T4954	5896-5900	UBERON:0000104	denotes	Life
T4955	5942-5953	CHEBI:465284	denotes	gancyclovir
T4956	6035-6039	SO:0000704	denotes	gene
T4957	6093-6100	SO:0001026	denotes	genomic
T4958	6117-6127	GO:0097617	denotes	hybridized
T4959	6136-6140	SO:0000147	denotes	Exon
T4960	6183-6187	SO:0000704	denotes	gene
T4961	6228-6236	CL:0002322	denotes	ES cells
T4962	6265-6276	UBERON:0000358	denotes	blastocysts
T4963	6297-6301	NCBITaxon:10088	denotes	mice
T4964	6480-6484	NCBITaxon:10088	denotes	mice
T4965	6568-6572	NCBITaxon:10088	denotes	mice
T4966	6611-6618	NCBITaxon:33208	denotes	animals
T4967	6663-6670	SO:0000704	denotes	genetic
T5781	8189-8193	NCBITaxon:10088	denotes	mice
T5782	8277-8279	PR:000006300	denotes	E2
T5783	8286-8295	SO:0000902	denotes	transgene
T5784	8309-8321	CHEBI:27902	denotes	tetracycline
T5785	8333-8337	NCBITaxon:10359	denotes	hCMV
T5786	8341-8349	SO:0000167	denotes	promoter
T5787	8369-8381	CHEBI:27902	denotes	tetracycline
T5788	8421-8425	NCBITaxon:10359	denotes	hCMV
T5789	8426-8434	SO:0000167	denotes	promoter
T5790	8494-8500	SO:0000188	denotes	intron
T5791	8532-8539	SO:0000673	denotes	message
T5792	8532-8539	CHEBI:33695	denotes	message
T5793	8554-8564	GO:0010467	denotes	expression
T5794	8582-8591	SO:0000993	denotes	consensus
T5795	8608-8624	SO:0000318	denotes	initiation codon
T5796	8637-8648	GO:0006412	denotes	translation
T5797	8659-8664	NCBITaxon:9606	denotes	human
T5798	8665-8667	PR:000006300	denotes	E2
T5799	8742-8747	PR:000000084	denotes	c-myc
T5800	8816-8820	NCBITaxon:10633	denotes	SV40
T5801	8826-8841	GO:0043631	denotes	polyadenylation
T5802	8826-8850	SO:0000610	denotes	polyadenylation sequence
T5803	8892-8903	GO:0006412	denotes	translation
T5804	8921-8923	PR:000006300	denotes	E2
T5805	8924-8933	SO:0000902	denotes	transgene
T5806	8952-8958	SO:0000440	denotes	vector
T5807	9003-9008	PR:P23940	denotes	BamHI
T5808	9065-9070	NCBITaxon:10088	denotes	mouse
T5809	9071-9078	UBERON:0000922	denotes	embryos
T5810	9193-9200	SO:0001026	denotes	Genomic
T5811	9214-9218	UBERON:0002415	denotes	tail
T5812	9222-9226	NCBITaxon:10088	denotes	mice
T5813	9301-9314	GO:0097617	denotes	hybridization
T5814	9326-9328	SO:0000028	denotes	bp
T5815	9352-9356	NCBITaxon:10633	denotes	SV40
T5816	9376-9378	PR:000006300	denotes	E2
T5817	9379-9388	SO:0000902	denotes	transgene
T6386	9423-9429	NCBITaxon:39107	denotes	murine
T6387	9452-9454	PR:000006300	denotes	E2
T6388	9486-9491	GO:0007618	denotes	mated
T6389	9509-9513	NCBITaxon:10088	denotes	mice
T6390	9550-9552	PR:000006300	denotes	E2
T6391	9570-9573	PR:000005308	denotes	LAP
T6392	9578-9587	SO:0000902	denotes	transgene
T6393	9710-9717	NCBITaxon:33208	denotes	animals
T6394	9750-9760	SO:0000902	denotes	transgenes
T6395	9808-9812	NCBITaxon:10088	denotes	mice
T6396	9856-9863	NCBITaxon:33208	denotes	animals
T6397	9929-9939	SO:0000902	denotes	transgenes
T6398	10117-10124	NCBITaxon:33208	denotes	animals
T6399	10139-10149	SO:0000902	denotes	transgenes
T6400	10175-10190	UBERON:0007221	denotes	neonatal period
T6657	10208-10212	NCBITaxon:10088	denotes	mice
T6658	10255-10262	SO:0001026	denotes	Genomic
T6659	10282-10286	UBERON:0002415	denotes	tail
T6660	10368-10375	CHEBI:2511	denotes	agarose
T6661	10408-10413	CHEBI:25614	denotes	nylon
T7141	10483-10488	NCBITaxon:10088	denotes	mouse
T7142	10489-10498	UBERON:0000922	denotes	embryonic
T7143	10499-10510	CL:0000057	denotes	fibroblasts
T7144	10530-10539	UBERON:0000922	denotes	embryonic
T7145	10582-10593	CL:0000057	denotes	Fibroblasts
T7146	10723-10734	CHEBI:9750	denotes	Triton X100
T7147	10882-10886	NCBITaxon:9925	denotes	goat
T7148	10887-10890	GO:0071735	denotes	IgG
T7149	10991-10993	PR:000006300	denotes	E2
T7150	11007-11012	UBERON:0001977	denotes	serum
T7151	11123-11131	GO:0042571	denotes	antibody
T7152	11263-11269	UBERON:0002107	denotes	livers
T7153	11424-11434	CHEBI:30362	denotes	isopentane
T7526	11582-11587	UBERON:0000178	denotes	Blood
T7527	11624-11629	UBERON:0001825	denotes	sinus
T7528	11633-11642	UBERON:0003481	denotes	tail vein
T7529	11646-11650	NCBITaxon:10088	denotes	mice
T7530	11700-11705	UBERON:0000178	denotes	blood
T7531	11733-11738	GO:0007567	denotes	natal
T7532	11768-11772	CHEBI:22918	denotes	BCAA
T7533	11798-11803	UBERON:0000178	denotes	blood
T8043	11913-11919	UBERON:0002107	denotes	Livers
T8044	12011-12017	UBERON:0002107	denotes	livers
T8045	12068-12075	CHEBI:17992	denotes	sucrose
T8046	12083-12087	CHEBI:9754	denotes	Tris
T8047	12088-12091	CHEBI:17883	denotes	HC1
T8048	12101-12106	UBERON:0002107	denotes	Liver
T8049	12248-12254	UBERON:0000479	denotes	tissue
T8050	12315-12320	UBERON:0002107	denotes	liver
T8051	12321-12327	UBERON:0000479	denotes	tissue
T8052	12421-12424	CHEBI:16526	denotes	CO2
T8053	12430-12436	_FRAGMENT	denotes	α-keto
T8054	12445-12456	CHEBI:17865	denotes	isocaproate
T8055	12440-12443	CHEBI:36927	denotes	14C
T8056	12509-12516	CHEBI:60004	denotes	mixture
T8057	12597-12614	CHEBI:17865	denotes	α-ketoisocaproate
T8058	12624-12629	CHEBI:15346	denotes	CoASH
T8059	12639-12660	CHEBI:9532	denotes	thiamin pyrophosphate
T8060	12667-12671	CHEBI:15846	denotes	NAD+
T8061	12678-12692	CHEBI:18320	denotes	dithiothreitol
T8062	12699-12703	CHEBI:18420	denotes	Mg2+
T8063	12734-12740	_FRAGMENT	denotes	α-keto
T8064	12749-12760	CHEBI:17865	denotes	isocaproate
T8065	12744-12747	CHEBI:36927	denotes	14C
T8066	12777-12782	UBERON:0002107	denotes	liver
T8067	12858-12861	CHEBI:16526	denotes	CO2
T8068	12877-12886	CHEBI:24651	denotes	hydroxide
T8069	12890-12897	CHEBI:31264	denotes	Hyamine
T8765	13041-13046	UBERON:0002107	denotes	liver
T8766	13130-13134	NCBITaxon:10088	denotes	mice
T8767	13204-13207	CHEBI:8984	denotes	SDS
T8768	13266-13270	CHEBI:53250	denotes	PVDF
T8769	13349-13351	PR:000006300	denotes	E2
T8770	13377-13383	NCBITaxon:9986	denotes	rabbit
T8771	13384-13386	PR:000006300	denotes	E2
T8772	13391-13395	UBERON:0001977	denotes	sera
T8773	13426-13431	NCBITaxon:10088	denotes	mouse
T8774	13445-13450	NCBITaxon:9606	denotes	human
T8775	13460-13471	PR:000006300	denotes	E2 subunits
T8776	13560-13566	NCBITaxon:9986	denotes	rabbit
T8777	13572-13577	PR:000000084	denotes	c-myc
T8778	13582-13590	GO:0042571	denotes	antibody
T8779	13677-13685	GO:0042571	denotes	antibody
T8780	13690-13697	PR:000003676	denotes	β-actin
T8781	13776-13780	NCBITaxon:9925	denotes	goat
T8782	13786-13792	NCBITaxon:9986	denotes	rabbit
T8783	13803-13811	GO:0042571	denotes	antibody
T8784	13812-13822	MOP:0000779	denotes	conjugated
T8785	13826-13837	NCBITaxon:3704	denotes	horseradish
T8786	13966-13973	CHEBI:33893	denotes	reagent
T9137	14054-14058	CHEBI:22918	denotes	BCAA
T10166	14254-14256	PR:000006300	denotes	E2
T10167	14257-14261	SO:0000704	denotes	gene
T10168	14271-14275	NCBITaxon:10088	denotes	mice
T10169	14286-14288	PR:000006300	denotes	E2
T10170	14298-14302	NCBITaxon:10088	denotes	mice
T10171	14312-14316	SO:0000704	denotes	gene
T10172	14330-14335	NCBITaxon:10088	denotes	mouse
T10173	14336-14344	CL:0002322	denotes	ES cells
T10174	14360-14362	PR:000006300	denotes	E2
T10175	14363-14367	SO:0000704	denotes	gene
T10176	14409-14411	PR:000006300	denotes	E2
T10177	14412-14416	SO:0000704	denotes	gene
T10178	14448-14452	SO:0000704	denotes	gene
T10179	14518-14525	SO:0001026	denotes	genomic
T10180	14552-14564	SO:0000852	denotes	part of Exon
T10181	14578-14582	SO:0000147	denotes	Exon
T10182	14636-14643	CL:0002322	denotes	ES cell
T10183	14733-14774	SO:0000193	denotes	restriction fragment length polymorphisms
T10184	14789-14793	SO:0000704	denotes	gene
T10185	14811-14813	PR:000006300	denotes	E2
T10186	14858-14860	PR:000006300	denotes	E2
T10187	14861-14865	SO:0000147	denotes	Exon
T10188	14930-14940	GO:0097617	denotes	hybridizes
T10189	14963-14983	SO:0000412	denotes	restriction fragment
T10190	15003-15009	SO:0001023	denotes	allele
T10191	15029-15036	CL:0002322	denotes	ES cell
T10192	15065-15073	CL:0002322	denotes	ES cells
T10193	15091-15101	GO:0097617	denotes	hybridizes
T10194	15119-15139	SO:0000412	denotes	restriction fragment
T10195	15257-15265	CL:0002322	denotes	ES cells
T10196	15290-15301	UBERON:0000358	denotes	blastocysts
T10197	15322-15326	NCBITaxon:10088	denotes	mice
T10198	15360-15364	NCBITaxon:10088	denotes	mice
T10199	15414-15420	SO:0001023	denotes	allele
T10200	15435-15439	NCBITaxon:10088	denotes	mice
T10201	15523-15530	NCBITaxon:33208	denotes	animals
T10202	15532-15536	NCBITaxon:10088	denotes	Mice
T10203	15583-15587	SO:0000147	denotes	Exon
T10204	15605-15615	GO:0097617	denotes	hybridized
T10205	15638-15658	SO:0000412	denotes	restriction fragment
T10206	15666-15670	NCBITaxon:10088	denotes	mice
T10207	15702-15706	NCBITaxon:10088	denotes	mice
T10208	15746-15750	NCBITaxon:10088	denotes	mice
T10209	15762-15766	NCBITaxon:10088	denotes	Mice
T10210	15786-15788	PR:000006300	denotes	E2
T10211	15803-15807	GO:0007567	denotes	born
T10212	15885-15892	GO:0007618	denotes	matings
T10213	15925-15929	NCBITaxon:10088	denotes	mice
T10214	16001-16008	NCBITaxon:33208	denotes	animals
T10215	16091-16093	PR:000006300	denotes	E2
T10216	16094-16098	SO:0000704	denotes	gene
T10217	16126-16135	UBERON:0000922	denotes	embryonic
T10218	16126-16147	GO:0009790	denotes	embryonic development
T10219	16193-16197	NCBITaxon:10088	denotes	mice
T10220	16198-16202	GO:0016265	denotes	died
T10221	16210-16226	UBERON:0012101	denotes	perinatal period
T10222	16214-16219	GO:0007567	denotes	natal
T10223	16250-16255	GO:0007567	denotes	birth
T10224	16371-16377	GO:0001967	denotes	suckle
T10225	16405-16410	GO:0007567	denotes	natal
T10226	16532-16543	UBERON:0001004	denotes	respiratory
T10227	16585-16589	GO:0016265	denotes	died
T10228	16609-16614	GO:0007567	denotes	birth
T10229	16671-16676	GO:0007567	denotes	natal
T12013	16748-16750	PR:000006300	denotes	E2
T12014	16761-16765	NCBITaxon:10088	denotes	mice
T12015	16820-16824	SO:0000704	denotes	gene
T12016	16856-16858	PR:000006300	denotes	E2
T12017	16864-16870	SO:0001023	denotes	allele
T12018	16904-16909	UBERON:0002107	denotes	liver
T12019	16929-16934	GO:0007567	denotes	natal
T12020	16941-16946	NCBITaxon:10088	denotes	mouse
T12021	16976-16982	GO:0007618	denotes	mating
T12022	17039-17043	NCBITaxon:10088	denotes	mice
T12023	17132-17137	NCBITaxon:10088	denotes	mouse
T12024	17138-17144	UBERON:0002107	denotes	livers
T12025	17180-17184	NCBITaxon:10088	denotes	mice
T12026	17280-17284	NCBITaxon:10088	denotes	mice
T12027	17317-17323	NCBITaxon:9606	denotes	humans
T12028	18214-18216	PR:000006300	denotes	E2
T12029	18226-18234	GO:0042571	denotes	antibody
T12030	18255-18257	PR:000006300	denotes	E2
T12031	18273-18277	NCBITaxon:10088	denotes	mice
T12032	18324-18326	PR:000006300	denotes	E2
T12033	18351-18356	UBERON:0002107	denotes	liver
T12034	18361-18370	UBERON:0000922	denotes	embryonic
T12035	18371-18382	CL:0000057	denotes	fibroblasts
T12036	18389-18393	NCBITaxon:10088	denotes	mice
T12037	18430-18432	PR:000006300	denotes	E2
T12038	18466-18473	UBERON:0000479	denotes	tissues
T12039	18481-18485	NCBITaxon:10088	denotes	mice
T12040	18498-18500	PR:000006300	denotes	E2
T12041	18510-18514	NCBITaxon:10088	denotes	mice
T12042	18547-18552	UBERON:0000178	denotes	blood
T12043	18569-18574	UBERON:0001088	denotes	urine
T12044	18602-18606	CHEBI:22918	denotes	BCAA
T12045	18760-18764	CHEBI:22918	denotes	BCAA
T12046	18856-18860	NCBITaxon:10088	denotes	mice
T12047	18866-18884	GO:0009081	denotes	metabolism of BCAA
T12048	18880-18884	CHEBI:22918	denotes	BCAA
T12049	18904-18924	GO:0006523	denotes	synthesis of alanine
T12050	18904-18916	_FRAGMENT	denotes	synthesis of
T12051	18926-18935	GO:0006537	denotes	glutamate
T12052	18941-18950	GO:0006542	denotes	glutamine
T12053	18977-18995	GO:0009081	denotes	metabolism of BCAA
T12054	18991-18995	CHEBI:22918	denotes	BCAA
T12055	19004-19008	NCBITaxon:10088	denotes	mice
T12056	19095-19100	UBERON:0000178	denotes	blood
T12057	19221-19225	NCBITaxon:10088	denotes	mice
T12058	19276-19280	NCBITaxon:10088	denotes	mice
T12059	19325-19329	NCBITaxon:10088	denotes	mice
T12060	19362-19366	NCBITaxon:10088	denotes	mice
T12061	19418-19423	UBERON:0000178	denotes	blood
T12062	19457-19462	UBERON:0000178	denotes	blood
T12063	19463-19467	CHEBI:22918	denotes	BCAA
T12064	19573-19577	CHEBI:22918	denotes	BCAA
T12065	19662-19666	CHEBI:22918	denotes	BCAA
T12066	19739-19743	CHEBI:22918	denotes	BCAA
T12067	19868-19873	UBERON:0000178	denotes	blood
T12077	20810-20814	NCBITaxon:10088	denotes	mice
T15482	29133-29139	UBERON:0002113	denotes	kidney
T15481	29126-29131	UBERON:0000955	denotes	brain
T15480	29113-29122	SO:0000902	denotes	transgene
T15479	29110-29112	PR:000006300	denotes	E2
T15478	29092-29102	GO:0010467	denotes	expression
T15477	29018-29020	PR:000006300	denotes	E2
T15476	29012-29017	NCBITaxon:10088	denotes	mouse
T15475	28985-28987	PR:000006300	denotes	E2
T15474	28979-28984	NCBITaxon:9606	denotes	Human
T19578	32979-32983	CHEBI:22918	denotes	BCAA
T19577	32913-32918	UBERON:0002107	denotes	liver
T19576	32858-32863	NCBITaxon:10088	denotes	mouse
T19575	32807-32816	UBERON:0000113	denotes	adulthood
T19574	32790-32794	NCBITaxon:10088	denotes	mice
T19573	32724-32728	NCBITaxon:10088	denotes	mice
T19572	32700-32705	UBERON:0002107	denotes	liver
T19571	32683-32692	SO:0000902	denotes	transgene
T19570	32680-32682	PR:000006300	denotes	E2
T19569	32674-32679	NCBITaxon:9606	denotes	human
T19568	32658-32668	GO:0010467	denotes	expression
T19567	32628-32643	UBERON:0007221	denotes	neonatal period
T19566	32607-32610	GO:0016265	denotes	die
T19565	32604-32606	PR:000006300	denotes	E2
T19564	32586-32595	SO:0000902	denotes	transgene
T19563	32565-32567	PR:000006300	denotes	E2
T19562	32539-32543	NCBITaxon:10088	denotes	mice
T19561	32527-32529	PR:000006300	denotes	E2
T19560	32518-32523	UBERON:0002107	denotes	liver
T19559	32508-32510	PR:000006300	denotes	E2
T19558	32502-32507	NCBITaxon:9606	denotes	human
T19557	32494-32501	GO:0010467	denotes	express
T19556	32355-32360	NCBITaxon:9606	denotes	human
T19555	32261-32266	NCBITaxon:10088	denotes	mouse
T19554	32121-32125	CHEBI:22918	denotes	BCAA
T19553	31950-31955	UBERON:0000955	denotes	brain
T19552	31909-31913	CHEBI:22918	denotes	BCAA
T19551	31841-31846	GO:0007567	denotes	birth
T19550	31817-31821	GO:0016265	denotes	died
T19549	31567-31577	UBERON:0001016	denotes	neurologic
T19548	31531-31542	UBERON:0001004	denotes	respiratory
T19547	31444-31454	UBERON:0001016	denotes	neurologic
T19546	31352-31357	NCBITaxon:10088	denotes	mouse
T19545	31282-31293	CL:0000057	denotes	fibroblasts
T19544	31272-31277	UBERON:0002107	denotes	liver
T21284	37704-37713	GO:0008152	denotes	metabolic
T21283	37649-37653	SO:0000704	denotes	gene
T21282	37505-37512	NCBITaxon:33208	denotes	animals
T21281	37445-37450	NCBITaxon:10088	denotes	mouse
T21280	37422-37433	SO:0000704	denotes	genetically
T21944	6693-6695	PR:000006300	denotes	E2
T21945	6696-6700	SO:0000704	denotes	gene
T21946	6710-6715	NCBITaxon:10088	denotes	mouse
T21947	6731-6735	SO:0000704	denotes	Gene
T21948	6778-6780	PR:000006300	denotes	E2
T21949	6790-6795	NCBITaxon:10088	denotes	mouse
T21950	6796-6804	CL:0002322	denotes	ES cells
T21951	6890-6902	SO:0000852	denotes	site in Exon
T21952	6924-6930	SO:0000188	denotes	intron
T21953	6948-6950	PR:000006300	denotes	E2
T21954	6951-6955	SO:0000704	denotes	gene
T21955	6980-7000	SO:0000412	denotes	restriction fragment
T21956	7006-7016	GO:0097617	denotes	hybridizes
T21957	7024-7028	SO:0000147	denotes	Exon
T21958	7068-7070	PR:000006300	denotes	E2
T21959	7100-7120	SO:0000412	denotes	restriction fragment
T21960	7126-7136	GO:0097617	denotes	hybridizes
T21961	7218-7234	SO:0001644	denotes	targeting vector
T21962	7265-7281	SO:0001644	denotes	targeting vector
T21963	7326-7333	SO:0001026	denotes	genomic
T21964	7374-7381	CL:0002322	denotes	ES cell
T21965	7417-7424	CL:0002322	denotes	ES cell
T21966	7512-7516	NCBITaxon:10088	denotes	mice
T21967	7531-7541	GO:0097617	denotes	hybridized
T21968	7550-7554	SO:0000147	denotes	Exon
T21969	7621-7626	UBERON:0002107	denotes	liver
T21970	7659-7661	PR:000006300	denotes	E2
T21971	7681-7686	GO:0007567	denotes	natal
T21972	7693-7698	NCBITaxon:10088	denotes	mouse
T21973	7731-7733	PR:000006300	denotes	E2
T21974	7743-7745	PR:000006300	denotes	E2
T21975	7755-7763	GO:0042571	denotes	antibody
T21976	7778-7785	GO:0005634	denotes	nuclear
T21977	7829-7831	PR:000006300	denotes	E2
T21978	7882-7887	NCBITaxon:10088	denotes	mouse
T21979	7967-7972	NCBITaxon:10088	denotes	mouse
T21980	7973-7982	UBERON:0000922	denotes	embryonic
T21981	7983-7994	CL:0000057	denotes	fibroblasts
T21982	8047-8049	PR:000006300	denotes	E2
T21983	8114-8126	GO:0005739	denotes	mitochondria
T22732	17406-17412	NCBITaxon:39107	denotes	murine
T22733	17448-17453	UBERON:0002107	denotes	liver
T22734	17540-17544	NCBITaxon:10088	denotes	mice
T22735	17595-17600	UBERON:0002107	denotes	liver
T22736	17662-17667	UBERON:0002107	denotes	liver
T22737	17678-17682	CHEBI:22918	denotes	BCAA
T22738	17701-17706	UBERON:0000178	denotes	blood
T22739	17710-17714	NCBITaxon:10088	denotes	mice
T22740	17722-17726	CHEBI:22918	denotes	BCAA
T22741	17787-17791	CHEBI:22918	denotes	BCAA
T22742	17810-17815	UBERON:0000178	denotes	blood
T22743	17825-17829	NCBITaxon:10088	denotes	mice
T22744	17901-17905	CHEBI:22918	denotes	BCAA
T22745	17920-17925	UBERON:0000178	denotes	blood
T22746	17929-17933	NCBITaxon:10088	denotes	mice
T22747	17980-17984	NCBITaxon:10088	denotes	mice
T22748	18009-18013	NCBITaxon:10088	denotes	mice
T22749	18063-18067	NCBITaxon:10088	denotes	mice
T23571	22586-22591	NCBITaxon:10088	denotes	mouse
T23570	22538-22545	NCBITaxon:33208	denotes	animals
T23569	22478-22482	NCBITaxon:10088	denotes	mice
T23568	22442-22444	PR:000006300	denotes	E2
T23567	22436-22441	NCBITaxon:9606	denotes	human
T23566	22406-22410	NCBITaxon:10088	denotes	mice
T23565	22367-22372	UBERON:0002107	denotes	liver
T23564	22353-22355	PR:000006300	denotes	E2
T23563	22319-22323	NCBITaxon:10088	denotes	mice
T23562	22231-22255	SO:0000610	denotes	polyadenylation sequence
T23561	22231-22246	GO:0043631	denotes	polyadenylation
T23560	22218-22222	NCBITaxon:10633	denotes	SV40
T23559	22195-22200	PR:000000084	denotes	c-myc
T23558	22165-22167	PR:000006300	denotes	E2
T23557	22159-22164	NCBITaxon:9606	denotes	human
T23556	22135-22141	SO:0000188	denotes	intron
T23555	22113-22121	SO:0000167	denotes	promoter
T23554	22062-22074	CHEBI:27902	denotes	tetracycline
T23553	22039-22048	SO:0000902	denotes	transgene
T23552	22036-22038	PR:000006300	denotes	E2
T23551	22018-22026	SO:0000167	denotes	promoter
T23550	22014-22017	PR:000005308	denotes	LAP
T23549	21999-22004	UBERON:0002107	denotes	liver
T23548	21958-21968	GO:0065007	denotes	controlled
T23547	21945-21957	CHEBI:27902	denotes	tetracycline
T23546	21933-21940	GO:0010467	denotes	express
T23545	21928-21932	NCBITaxon:10088	denotes	mice
T23544	21880-21884	NCBITaxon:10088	denotes	mice
T23543	21861-21864	PR:000005308	denotes	LAP
T23542	21857-21859	PR:000006300	denotes	E2
T23541	21851-21856	NCBITaxon:9606	denotes	human
T23540	21843-21850	GO:0010467	denotes	express
T23539	21833-21837	NCBITaxon:10088	denotes	mice
T23538	21755-21760	NCBITaxon:10088	denotes	mouse
T24769	20000-20005	UBERON:0000178	denotes	blood
T24770	20158-20163	GO:0007567	denotes	birth
T3109	292-296	CHEBI:22918	denotes	BCAA
T3110	674-678	CHEBI:22918	denotes	BCAA
T3111	682-687	UBERON:0000178	denotes	blood
T3100	11-16	NCBITaxon:4022	denotes	Maple
T3101	23-28	UBERON:0001088	denotes	Urine
T3102	49-56	SO:0000704	denotes	genetic
T3103	107-116	CHEBI:25754	denotes	keto acid
T3104	142-155	GO:0005739	denotes	mitochondrial
T3105	168-175	GO:0032991	denotes	complex
T3106	196-205	MOP:0000568	denotes	oxidative
T3107	240-250	CHEBI:25754	denotes	keto acids
T3108	264-290	CHEBI:22918	denotes	branched-chain amino acids
T3112	698-709	UBERON:0006314	denotes	body fluids
T3113	986-990	CHEBI:22918	denotes	BCAA
T3114	1120-1125	UBERON:0000178	denotes	blood
T3115	1126-1130	CHEBI:22918	denotes	BCAA
T3116	1357-1370	GO:0017086	denotes	BCKDH complex
T3117	1464-1477	CHEBI:50488	denotes	dihydrolipoyl
T3118	1492-1494	PR:000006300	denotes	E2
T3119	1503-1516	CHEBI:50488	denotes	dihydrolipoyl
T3121	1590-1591	_FRAGMENT	denotes	α
T3122	1602-1610	PR:000004686	denotes	subunits
T15423	26333-26334	UBERON:0000178	denotes	d
T15422	26329-26330	CHEBI:22918	denotes	A
T15421	26323-26324	PR:000005308	denotes	L
T15420	25099-25106	NCBITaxon:33208	denotes	animals
T15419	24955-24957	PR:000006300	denotes	E2
T15418	24865-24874	SO:0000902	denotes	transgene
T15417	24734-24738	NCBITaxon:10088	denotes	mice
T15416	24553-24557	NCBITaxon:10088	denotes	mice
T15415	24501-24511	SO:0000902	denotes	transgenes
T15414	24467-24469	PR:000006300	denotes	E2
T15413	24416-24423	NCBITaxon:33208	denotes	animals
T15412	24251-24261	SO:0000902	denotes	transgenes
T15411	24193-24195	PR:000006300	denotes	E2
T15410	24174-24183	SO:0000902	denotes	transgene
T15409	24171-24173	PR:000006300	denotes	E2
T15408	24152-24161	SO:0000902	denotes	transgene
T15407	24144-24147	PR:000005308	denotes	LAP
T15406	24113-24117	NCBITaxon:10088	denotes	mice
T15405	24050-24052	PR:000006300	denotes	E2
T15404	24010-24019	SO:0000902	denotes	transgene
T15403	24002-24005	PR:000005308	denotes	LAP
T15402	23970-23974	NCBITaxon:10088	denotes	mice
T15401	23900-23904	NCBITaxon:10088	denotes	mice
T15400	23897-23899	PR:000006300	denotes	E2
T15399	23855-23859	UBERON:0002415	denotes	tail
T15398	23792-23801	SO:0000902	denotes	transgene
T15397	23569-23584	SO:0000366	denotes	insertion sites
T15396	23559-23568	SO:0000902	denotes	transgene
T15395	23538-23545	NCBITaxon:33208	denotes	animals
T15394	23445-23454	SO:0000902	denotes	transgene
T15393	23256-23265	SO:0000902	denotes	transgene
T15392	23194-23203	SO:0000902	denotes	transgene
T15391	23191-23193	PR:000006300	denotes	E2
T15390	23164-23168	NCBITaxon:10088	denotes	mice
T15389	23107-23117	GO:0045120	denotes	Pronuclear
T15388	23071-23072	NCBITaxon:10088	denotes	i
T15387	23056-23057	UBERON:0002113	denotes	d
T15386	23055-23056	NCBITaxon:10088	denotes	e
T15385	23053-23054	NCBITaxon:9606	denotes	u
T15384	23052-23053	GO:0042571	denotes	d
T15383	23041-23042	UBERON:0002107	denotes	v
T15382	23028-23032	NCBITaxon:10088	denotes	mice
T15381	23020-23023	PR:000005308	denotes	LAP
T15431	26818-26822	NCBITaxon:10088	denotes	mice
T15430	26745-26750	UBERON:0000178	denotes	Blood
T15429	26675-26679	NCBITaxon:10088	denotes	mice
T15428	26636-26640	CHEBI:22918	denotes	BCAA
T15427	26515-26519	NCBITaxon:10088	denotes	mice
T15426	26491-26495	CHEBI:22918	denotes	BCAA
T15425	26470-26474	CHEBI:22918	denotes	BCAA
T15424	26414-26419	UBERON:0000178	denotes	blood
R339	T3122	T3121	_lexicallyChainedTo	subunits,α
R340	T3128	T3127	_lexicallyChainedTo	dehydrogenase complexes,pyruvate
R341	T3174	T3173	_lexicallyChainedTo	cells,embryonic stem
R342	T3174	T3175	_lexicallyChainedTo	cells,ES
R2278	T8054	T8053	_lexicallyChainedTo	isocaproate,α-keto
R2279	T8064	T8063	_lexicallyChainedTo	isocaproate,α-keto
R3286	T12051	T12050	_lexicallyChainedTo	glutamate,synthesis of
R3287	T12052	T12050	_lexicallyChainedTo	glutamine,synthesis of
R3833	T15441	T15440	_lexicallyChainedTo	protein,production of

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