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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. 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). The reason these two lines were unresponsive to doxycycline is unknown. It is conceivable that the integration site of the transgenes was not permissive for regulated expression. Screening of additional lines may be needed to find lines that allow for survival and can also be regulated."}
craft-ca-core-ex-dev
{"project":"craft-ca-core-ex-dev","denotations":[{"id":"T19765","span":{"begin":889,"end":898},"obj":"GO:0065007"},{"id":"T19764","span":{"begin":779,"end":789},"obj":"GO:0010467"},{"id":"T19763","span":{"begin":769,"end":778},"obj":"GO:0065007"},{"id":"T19762","span":{"begin":735,"end":745},"obj":"SO_EXT:0000902"},{"id":"T19761","span":{"begin":711,"end":727},"obj":"SO_EXT:0000366"},{"id":"T19760","span":{"begin":660,"end":671},"obj":"CHEBI:50845"},{"id":"T19759","span":{"begin":570,"end":580},"obj":"SO_EXT:transgenic_entity"},{"id":"T19758","span":{"begin":537,"end":548},"obj":"CHEBI:50845"},{"id":"T19757","span":{"begin":514,"end":526},"obj":"CHEBI:27902"},{"id":"T19756","span":{"begin":491,"end":499},"obj":"SO_EXT:0005853"},{"id":"T19755","span":{"begin":480,"end":490},"obj":"GO:0010467"},{"id":"T19754","span":{"begin":477,"end":479},"obj":"PR_EXT:000006300"},{"id":"T19753","span":{"begin":471,"end":476},"obj":"NCBITaxon:9606"},{"id":"T19752","span":{"begin":407,"end":416},"obj":"SO_EXT:0000902"},{"id":"T19751","span":{"begin":398,"end":406},"obj":"SO_EXT:sequence_rescue_process"},{"id":"T19750","span":{"begin":256,"end":260},"obj":"NCBITaxon:10088"},{"id":"T19749","span":{"begin":116,"end":120},"obj":"SO_EXT:0000704"},{"id":"T19748","span":{"begin":106,"end":115},"obj":"GO:0065007"},{"id":"T19747","span":{"begin":93,"end":105},"obj":"CHEBI:27902"},{"id":"T19746","span":{"begin":4,"end":14},"obj":"SO_EXT:transgenic_entity"}],"text":"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]. 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. 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). The reason these two lines were unresponsive to doxycycline is unknown. It is conceivable that the integration site of the transgenes was not permissive for regulated expression. Screening of additional lines may be needed to find lines that allow for survival and can also be regulated."}
craft-ca-core-dev
{"project":"craft-ca-core-dev","denotations":[{"id":"T19604","span":{"begin":889,"end":898},"obj":"GO:0065007"},{"id":"T19603","span":{"begin":779,"end":789},"obj":"GO:0010467"},{"id":"T19602","span":{"begin":769,"end":778},"obj":"GO:0065007"},{"id":"T19601","span":{"begin":735,"end":745},"obj":"SO:0000902"},{"id":"T19600","span":{"begin":711,"end":727},"obj":"SO:0000366"},{"id":"T19599","span":{"begin":660,"end":671},"obj":"CHEBI:50845"},{"id":"T19598","span":{"begin":537,"end":548},"obj":"CHEBI:50845"},{"id":"T19597","span":{"begin":514,"end":526},"obj":"CHEBI:27902"},{"id":"T19596","span":{"begin":491,"end":499},"obj":"SO:0005853"},{"id":"T19595","span":{"begin":480,"end":490},"obj":"GO:0010467"},{"id":"T19594","span":{"begin":477,"end":479},"obj":"PR:000006300"},{"id":"T19593","span":{"begin":471,"end":476},"obj":"NCBITaxon:9606"},{"id":"T19592","span":{"begin":407,"end":416},"obj":"SO:0000902"},{"id":"T19591","span":{"begin":256,"end":260},"obj":"NCBITaxon:10088"},{"id":"T19590","span":{"begin":116,"end":120},"obj":"SO:0000704"},{"id":"T19589","span":{"begin":106,"end":115},"obj":"GO:0065007"},{"id":"T19588","span":{"begin":93,"end":105},"obj":"CHEBI:27902"}],"text":"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]. 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. 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). The reason these two lines were unresponsive to doxycycline is unknown. It is conceivable that the integration site of the transgenes was not permissive for regulated expression. Screening of additional lines may be needed to find lines that allow for survival and can also be regulated."}