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Id Subject Object Predicate Lexical cue
T2571 13-16 NN denotes p53
T2572 17-19 VBZ denotes is
T2573 20-23 CD denotes one
T2574 24-26 IN denotes of
T2575 27-30 DT denotes the
T2576 52-60 NN denotes proteins
T2577 31-35 RBS denotes most
T2578 36-42 RB denotes highly
T2579 43-51 JJ denotes analyzed
T2580 61-64 IN denotes for
T2581 65-68 DT denotes the
T2582 77-82 NNS denotes years
T2583 69-73 JJ denotes past
T2584 74-76 CD denotes 25
T2585 82-83 . denotes .
T2586 83-245 sentence denotes Studies in cultured cells, often relying on the transfection of plasmids expressing various p53 mutants, have established models to explain how p53 is regulated.
T2587 84-91 NNS denotes Studies
T2588 194-205 VBN denotes established
T2589 92-94 IN denotes in
T2590 95-103 VBN denotes cultured
T2591 104-109 NNS denotes cells
T2592 109-111 , denotes ,
T2593 111-116 RB denotes often
T2594 117-124 VBG denotes relying
T2595 125-127 IN denotes on
T2596 128-131 DT denotes the
T2597 132-144 NN denotes transfection
T2598 145-147 IN denotes of
T2599 148-156 NNS denotes plasmids
T2600 157-167 VBG denotes expressing
T2601 168-175 JJ denotes various
T2602 180-187 NNS denotes mutants
T2603 176-179 NN denotes p53
T2604 187-189 , denotes ,
T2605 189-193 VBD denotes have
T2606 206-212 NNS denotes models
T2607 213-215 TO denotes to
T2608 216-223 VB denotes explain
T2609 224-227 WRB denotes how
T2610 235-244 VBN denotes regulated
T2611 228-231 NN denotes p53
T2612 232-234 VBZ denotes is
T2613 244-245 . denotes .
T2614 245-435 sentence denotes In recent years, some of these models were tested in vivo by targeting subtle mutations at the p53 locus using homologous recombination in embryonic stem (ES) cells to generate mutant mice.
T2615 246-248 IN denotes In
T2616 289-295 VBN denotes tested
T2617 249-255 JJ denotes recent
T2618 256-261 NNS denotes years
T2619 261-263 , denotes ,
T2620 263-267 DT denotes some
T2621 268-270 IN denotes of
T2622 271-276 DT denotes these
T2623 277-283 NNS denotes models
T2624 284-288 VBD denotes were
T2625 296-298 FW denotes in
T2626 299-303 FW denotes vivo
T2627 304-306 IN denotes by
T2628 307-316 VBG denotes targeting
T2629 317-323 JJ denotes subtle
T2630 324-333 NNS denotes mutations
T2631 334-336 IN denotes at
T2632 337-340 DT denotes the
T2633 345-350 NN denotes locus
T2634 341-344 NN denotes p53
T2635 351-356 VBG denotes using
T2636 357-367 JJ denotes homologous
T2637 368-381 NN denotes recombination
T2638 382-384 IN denotes in
T2639 385-394 JJ denotes embryonic
T2640 395-399 NN denotes stem
T2641 405-410 NNS denotes cells
T2642 400-401 -LRB- denotes (
T2643 401-403 NN denotes ES
T2644 403-404 -RRB- denotes )
T2645 411-413 TO denotes to
T2646 414-422 VB denotes generate
T2647 423-429 JJ denotes mutant
T2648 430-434 NNS denotes mice
T2649 434-435 . denotes .
T2650 435-638 sentence denotes The strength of this approach is that mutations are tested in a genomic setting and expressed from the endogenous promoter, ensuring physiological expression levels and correct spatio-temporal profiles.
T2651 436-439 DT denotes The
T2652 440-448 NN denotes strength
T2653 466-468 VBZ denotes is
T2654 449-451 IN denotes of
T2655 452-456 DT denotes this
T2656 457-465 NN denotes approach
T2657 469-473 IN denotes that
T2658 488-494 VBN denotes tested
T2659 474-483 NNS denotes mutations
T2660 484-487 VBP denotes are
T2661 495-497 IN denotes in
T2662 498-499 DT denotes a
T2663 508-515 NN denotes setting
T2664 500-507 JJ denotes genomic
T2665 516-519 CC denotes and
T2666 520-529 VBN denotes expressed
T2667 530-534 IN denotes from
T2668 535-538 DT denotes the
T2669 550-558 NN denotes promoter
T2670 539-549 JJ denotes endogenous
T2671 558-560 , denotes ,
T2672 560-568 VBG denotes ensuring
T2673 569-582 JJ denotes physiological
T2674 594-600 NNS denotes levels
T2675 583-593 NN denotes expression
T2676 601-604 CC denotes and
T2677 605-612 JJ denotes correct
T2678 629-637 NNS denotes profiles
T2679 613-619 JJ denotes spatio
T2680 620-628 JJ denotes temporal
T2681 619-620 HYPH denotes -
T2682 637-638 . denotes .
T2683 638-904 sentence denotes As significant differences between phenotypes from targeted p53 mutants in vivo and transfection data were observed [e.g. Refs (1–5)], more targeted mutations need to be generated and analyzed in multiple tissues to formulate more accurate models of p53 regulation.
T2684 639-641 IN denotes As
T2685 746-754 VBN denotes observed
T2686 642-653 JJ denotes significant
T2687 654-665 NNS denotes differences
T2688 666-673 IN denotes between
T2689 674-684 NNS denotes phenotypes
T2690 685-689 IN denotes from
T2691 690-698 VBN denotes targeted
T2692 703-710 NNS denotes mutants
T2693 699-702 NN denotes p53
T2694 711-713 FW denotes in
T2695 714-718 FW denotes vivo
T2696 719-722 CC denotes and
T2697 723-735 NN denotes transfection
T2698 736-740 NNS denotes data
T2699 741-745 VBD denotes were
T2700 798-802 VBP denotes need
T2701 755-756 -LRB- denotes [
T2702 767-768 CD denotes 1
T2703 756-760 FW denotes e.g.
T2704 761-765 NNS denotes Refs
T2705 766-767 -LRB- denotes (
T2706 768-769 SYM denotes –
T2707 769-770 CD denotes 5
T2708 770-771 -RRB- denotes )
T2709 771-772 -RRB- denotes ]
T2710 772-774 , denotes ,
T2711 774-778 RBR denotes more
T2712 779-787 VBN denotes targeted
T2713 788-797 NNS denotes mutations
T2714 803-805 TO denotes to
T2715 809-818 VBN denotes generated
T2716 806-808 VB denotes be
T2717 819-822 CC denotes and
T2718 823-831 VBN denotes analyzed
T2719 832-834 IN denotes in
T2720 835-843 JJ denotes multiple
T2721 844-851 NNS denotes tissues
T2722 852-854 TO denotes to
T2723 855-864 VB denotes formulate
T2724 865-869 RBR denotes more
T2725 870-878 JJ denotes accurate
T2726 879-885 NNS denotes models
T2727 886-888 IN denotes of
T2728 889-892 NN denotes p53
T2729 893-903 NN denotes regulation
T2730 903-904 . denotes .
T2731 904-1425 sentence denotes However, using homologous recombination in ES cells to generate mutant mice is an inefficient, slow and expensive method because (i) homologous recombination typically occurs at low frequency in ES cells, requiring sophisticated selection schemes and screening of hundreds of clones to identify the desired mutant; (ii) large (15–20 kb) plasmids, often difficult to clone, are required to increase targeting efficiency and (iii) breeding mice to homozygosity and housing a mouse colony generate further delays and costs.
T2732 905-912 RB denotes However
T2733 981-983 VBZ denotes is
T2734 912-914 , denotes ,
T2735 914-919 VBG denotes using
T2736 920-930 JJ denotes homologous
T2737 931-944 NN denotes recombination
T2738 945-947 IN denotes in
T2739 948-950 NN denotes ES
T2740 951-956 NNS denotes cells
T2741 957-959 TO denotes to
T2742 960-968 VB denotes generate
T2743 969-975 JJ denotes mutant
T2744 976-980 NNS denotes mice
T2745 984-986 DT denotes an
T2746 1019-1025 NN denotes method
T2747 987-998 JJ denotes inefficient
T2748 998-1000 , denotes ,
T2749 1000-1004 JJ denotes slow
T2750 1005-1008 CC denotes and
T2751 1009-1018 JJ denotes expensive
T2752 1026-1033 IN denotes because
T2753 1073-1079 VBZ denotes occurs
T2754 1034-1035 -LRB- denotes (
T2755 1035-1036 LS denotes i
T2756 1036-1037 -RRB- denotes )
T2757 1038-1048 JJ denotes homologous
T2758 1049-1062 NN denotes recombination
T2759 1063-1072 RB denotes typically
T2760 1080-1082 IN denotes at
T2761 1083-1086 JJ denotes low
T2762 1087-1096 NN denotes frequency
T2763 1097-1099 IN denotes in
T2764 1100-1102 NN denotes ES
T2765 1103-1108 NNS denotes cells
T2766 1108-1110 , denotes ,
T2767 1110-1119 VBG denotes requiring
T2768 1120-1133 JJ denotes sophisticated
T2769 1144-1151 NNS denotes schemes
T2770 1134-1143 NN denotes selection
T2771 1152-1155 CC denotes and
T2772 1156-1165 NN denotes screening
T2773 1166-1168 IN denotes of
T2774 1169-1177 NNS denotes hundreds
T2775 1178-1180 IN denotes of
T2776 1181-1187 NNS denotes clones
T2777 1188-1190 TO denotes to
T2778 1191-1199 VB denotes identify
T2779 1200-1203 DT denotes the
T2780 1212-1218 NN denotes mutant
T2781 1204-1211 JJ denotes desired
T2782 1218-1219 : denotes ;
T2783 1220-1221 -LRB- denotes (
T2784 1221-1223 LS denotes ii
T2785 1242-1250 NNS denotes plasmids
T2786 1223-1224 -RRB- denotes )
T2787 1225-1230 JJ denotes large
T2788 1231-1232 -LRB- denotes (
T2789 1238-1240 NN denotes kb
T2790 1232-1234 CD denotes 15
T2791 1235-1237 CD denotes 20
T2792 1234-1235 SYM denotes –
T2793 1240-1241 -RRB- denotes )
T2794 1282-1290 VBN denotes required
T2795 1250-1252 , denotes ,
T2796 1252-1257 RB denotes often
T2797 1258-1267 JJ denotes difficult
T2798 1268-1270 TO denotes to
T2799 1271-1276 VB denotes clone
T2800 1276-1278 , denotes ,
T2801 1278-1281 VBP denotes are
T2802 1291-1293 TO denotes to
T2803 1294-1302 VB denotes increase
T2804 1303-1312 VBG denotes targeting
T2805 1313-1323 NN denotes efficiency
T2806 1324-1327 CC denotes and
T2807 1328-1329 -LRB- denotes (
T2808 1329-1332 LS denotes iii
T2809 1391-1399 VBP denotes generate
T2810 1332-1333 -RRB- denotes )
T2811 1334-1342 VBG denotes breeding
T2812 1343-1347 NNS denotes mice
T2813 1348-1350 IN denotes to
T2814 1351-1363 NN denotes homozygosity
T2815 1364-1367 CC denotes and
T2816 1368-1375 VBG denotes housing
T2817 1376-1377 DT denotes a
T2818 1384-1390 NN denotes colony
T2819 1378-1383 NN denotes mouse
T2820 1400-1407 JJ denotes further
T2821 1408-1414 NNS denotes delays
T2822 1415-1418 CC denotes and
T2823 1419-1424 NNS denotes costs
T2824 1424-1425 . denotes .
T2825 1425-1539 sentence denotes Such limitations make the repeated targeting of a locus a technically daunting and economically impractical task.
T2826 1426-1430 JJ denotes Such
T2827 1431-1442 NNS denotes limitations
T2828 1443-1447 VBP denotes make
T2829 1448-1451 DT denotes the
T2830 1461-1470 NN denotes targeting
T2831 1452-1460 VBN denotes repeated
T2832 1534-1538 NN denotes task
T2833 1471-1473 IN denotes of
T2834 1474-1475 DT denotes a
T2835 1476-1481 NN denotes locus
T2836 1482-1483 DT denotes a
T2837 1484-1495 RB denotes technically
T2838 1496-1504 VBG denotes daunting
T2839 1505-1508 CC denotes and
T2840 1509-1521 RB denotes economically
T2841 1522-1533 JJ denotes impractical
T2842 1538-1539 . denotes .
T2843 1539-1652 sentence denotes Improvements in current technologies are needed to enable such analyses to be applied to the p53 or other genes.
T2844 1540-1552 NNS denotes Improvements
T2845 1581-1587 VBN denotes needed
T2846 1553-1555 IN denotes in
T2847 1556-1563 JJ denotes current
T2848 1564-1576 NNS denotes technologies
T2849 1577-1580 VBP denotes are
T2850 1588-1590 TO denotes to
T2851 1591-1597 VB denotes enable
T2852 1598-1602 JJ denotes such
T2853 1603-1611 NNS denotes analyses
T2854 1612-1614 TO denotes to
T2855 1618-1625 VBN denotes applied
T2856 1615-1617 VB denotes be
T2857 1626-1628 IN denotes to
T2858 1629-1632 DT denotes the
T2859 1633-1636 NN denotes p53
T2860 1637-1639 CC denotes or
T2861 1640-1645 JJ denotes other
T2862 1646-1651 NNS denotes genes
T2863 1651-1652 . denotes .
T2864 1652-1746 sentence denotes Developing methods to increase targeting efficiency in ES cells is clearly an important goal.
T2865 1653-1663 VBG denotes Developing
T2866 1717-1719 VBZ denotes is
T2867 1664-1671 NNS denotes methods
T2868 1672-1674 TO denotes to
T2869 1675-1683 VB denotes increase
T2870 1684-1693 VBG denotes targeting
T2871 1694-1704 NN denotes efficiency
T2872 1705-1707 IN denotes in
T2873 1708-1710 NN denotes ES
T2874 1711-1716 NNS denotes cells
T2875 1720-1727 RB denotes clearly
T2876 1728-1730 DT denotes an
T2877 1741-1745 NN denotes goal
T2878 1731-1740 JJ denotes important
T2879 1745-1746 . denotes .
T2880 1746-1847 sentence denotes In addition, efficient methods for gene targeting in fibroblasts could expedite phenotypic analyses.
T2881 1747-1749 IN denotes In
T2882 1818-1826 VB denotes expedite
T2883 1750-1758 NN denotes addition
T2884 1758-1760 , denotes ,
T2885 1760-1769 JJ denotes efficient
T2886 1770-1777 NNS denotes methods
T2887 1778-1781 IN denotes for
T2888 1782-1786 NN denotes gene
T2889 1787-1796 NN denotes targeting
T2890 1797-1799 IN denotes in
T2891 1800-1811 NNS denotes fibroblasts
T2892 1812-1817 MD denotes could
T2893 1827-1837 JJ denotes phenotypic
T2894 1838-1846 NNS denotes analyses
T2895 1846-1847 . denotes .
T2896 1847-1957 sentence denotes Indeed, siRNAs in fibroblasts often provide a faster read-out than equivalent gene knock-outs in animals (6).
T2897 1848-1854 RB denotes Indeed
T2898 1884-1891 VBP denotes provide
T2899 1854-1856 , denotes ,
T2900 1856-1862 NNS denotes siRNAs
T2901 1863-1865 IN denotes in
T2902 1866-1877 NNS denotes fibroblasts
T2903 1878-1883 RB denotes often
T2904 1892-1893 DT denotes a
T2905 1906-1909 NN denotes out
T2906 1894-1900 JJR denotes faster
T2907 1901-1905 NN denotes read
T2908 1905-1906 HYPH denotes -
T2909 1910-1914 IN denotes than
T2910 1915-1925 JJ denotes equivalent
T2911 1937-1941 NNS denotes outs
T2912 1926-1930 NN denotes gene
T2913 1931-1936 NN denotes knock
T2914 1936-1937 HYPH denotes -
T2915 1942-1944 IN denotes in
T2916 1945-1952 NNS denotes animals
T2917 1953-1954 -LRB- denotes (
T2918 1954-1955 CD denotes 6
T2919 1955-1956 -RRB- denotes )
T2920 1956-1957 . denotes .
T2921 1957-2093 sentence denotes However, modeling most disease-associated mutations requires generating subtle mutations, not knock-outs or reduced expression alleles.
T2922 1958-1965 RB denotes However
T2923 2010-2018 VBZ denotes requires
T2924 1965-1967 , denotes ,
T2925 1967-1975 VBG denotes modeling
T2926 1976-1980 RBS denotes most
T2927 2000-2009 NNS denotes mutations
T2928 1981-1988 NN denotes disease
T2929 1989-1999 JJ denotes associated
T2930 1988-1989 HYPH denotes -
T2931 2019-2029 VBG denotes generating
T2932 2030-2036 JJ denotes subtle
T2933 2037-2046 NNS denotes mutations
T2934 2046-2048 , denotes ,
T2935 2048-2051 CC denotes not
T2936 2052-2057 NN denotes knock
T2937 2058-2062 NNS denotes outs
T2938 2057-2058 HYPH denotes -
T2939 2063-2065 CC denotes or
T2940 2066-2073 VBN denotes reduced
T2941 2074-2084 NN denotes expression
T2942 2085-2092 NNS denotes alleles
T2943 2092-2093 . denotes .
T2944 2093-2285 sentence denotes Targeting point mutations in fibroblasts by homologous recombination is extremely inefficient, and targeting both alleles is required to reveal the phenotype of recessive autosomal mutations.
T2945 2094-2103 VBG denotes Targeting
T2946 2163-2165 VBZ denotes is
T2947 2104-2109 NN denotes point
T2948 2110-2119 NNS denotes mutations
T2949 2120-2122 IN denotes in
T2950 2123-2134 NNS denotes fibroblasts
T2951 2135-2137 IN denotes by
T2952 2138-2148 JJ denotes homologous
T2953 2149-2162 NN denotes recombination
T2954 2166-2175 RB denotes extremely
T2955 2176-2187 JJ denotes inefficient
T2956 2187-2189 , denotes ,
T2957 2189-2192 CC denotes and
T2958 2193-2202 VBG denotes targeting
T2959 2219-2227 VBN denotes required
T2960 2203-2207 DT denotes both
T2961 2208-2215 NNS denotes alleles
T2962 2216-2218 VBZ denotes is
T2963 2228-2230 TO denotes to
T2964 2231-2237 VB denotes reveal
T2965 2238-2241 DT denotes the
T2966 2242-2251 NN denotes phenotype
T2967 2252-2254 IN denotes of
T2968 2255-2264 JJ denotes recessive
T2969 2265-2274 JJ denotes autosomal
T2970 2275-2284 NNS denotes mutations
T2971 2284-2285 . denotes .
T2972 2285-2403 sentence denotes Here we report an approach that enables highly efficient targeting at the p53 locus in both ES cells and fibroblasts.
T2973 2286-2290 RB denotes Here
T2974 2294-2300 VBP denotes report
T2975 2291-2293 PRP denotes we
T2976 2301-2303 DT denotes an
T2977 2304-2312 NN denotes approach
T2978 2313-2317 WDT denotes that
T2979 2318-2325 VBZ denotes enables
T2980 2326-2332 RB denotes highly
T2981 2333-2342 JJ denotes efficient
T2982 2343-2352 NN denotes targeting
T2983 2353-2355 IN denotes at
T2984 2356-2359 DT denotes the
T2985 2364-2369 NN denotes locus
T2986 2360-2363 NN denotes p53
T2987 2370-2372 IN denotes in
T2988 2373-2377 CC denotes both
T2989 2381-2386 NNS denotes cells
T2990 2378-2380 NN denotes ES
T2991 2387-2390 CC denotes and
T2992 2391-2402 NNS denotes fibroblasts
T2993 2402-2403 . denotes .
T2994 2403-2699 sentence denotes Recombinase-Mediated Cassette Exchange (RMCE) approaches were developed to improve targeting efficiency using a two-step process: the gene of interest is first replaced by a selection cassette flanked by recombinase target sites (e.g. loxP sites for Cre recombinase, to create a ‘floxed’ locus).
T2995 2404-2415 NN denotes Recombinase
T2996 2416-2424 JJ denotes Mediated
T2997 2415-2416 HYPH denotes -
T2998 2434-2442 NNP denotes Exchange
T2999 2425-2433 NNP denotes Cassette
T3000 2450-2460 NNS denotes approaches
T3001 2443-2444 -LRB- denotes (
T3002 2444-2448 NN denotes RMCE
T3003 2448-2449 -RRB- denotes )
T3004 2466-2475 VBN denotes developed
T3005 2461-2465 VBD denotes were
T3006 2564-2572 VBN denotes replaced
T3007 2476-2478 TO denotes to
T3008 2479-2486 VB denotes improve
T3009 2487-2496 VBG denotes targeting
T3010 2497-2507 NN denotes efficiency
T3011 2508-2513 VBG denotes using
T3012 2514-2515 DT denotes a
T3013 2525-2532 NN denotes process
T3014 2516-2519 CD denotes two
T3015 2520-2524 NN denotes step
T3016 2519-2520 HYPH denotes -
T3017 2532-2534 : denotes :
T3018 2534-2537 DT denotes the
T3019 2538-2542 NN denotes gene
T3020 2543-2545 IN denotes of
T3021 2546-2554 NN denotes interest
T3022 2555-2557 VBZ denotes is
T3023 2558-2563 RB denotes first
T3024 2573-2575 IN denotes by
T3025 2576-2577 DT denotes a
T3026 2588-2596 NN denotes cassette
T3027 2578-2587 NN denotes selection
T3028 2597-2604 VBN denotes flanked
T3029 2605-2607 IN denotes by
T3030 2608-2619 NN denotes recombinase
T3031 2627-2632 NNS denotes sites
T3032 2620-2626 NN denotes target
T3033 2633-2634 -LRB- denotes (
T3034 2644-2649 NNS denotes sites
T3035 2634-2638 FW denotes e.g.
T3036 2639-2643 NN denotes loxP
T3037 2650-2653 IN denotes for
T3038 2654-2657 NN denotes Cre
T3039 2658-2669 NN denotes recombinase
T3040 2669-2671 , denotes ,
T3041 2671-2673 TO denotes to
T3042 2674-2680 VB denotes create
T3043 2681-2682 DT denotes a
T3044 2692-2697 NN denotes locus
T3045 2683-2684 `` denotes ‘
T3046 2684-2690 JJ denotes floxed
T3047 2690-2691 '' denotes ’
T3048 2697-2698 -RRB- denotes )
T3049 2698-2699 . denotes .
T3050 2699-2859 sentence denotes Then, Cre-mediated recombination in the presence of a cassette containing a floxed mutant allele removes the resident sequence and inserts the mutant gene (7).
T3051 2700-2704 RB denotes Then
T3052 2797-2804 VBZ denotes removes
T3053 2704-2706 , denotes ,
T3054 2706-2709 NN denotes Cre
T3055 2710-2718 JJ denotes mediated
T3056 2709-2710 HYPH denotes -
T3057 2719-2732 NN denotes recombination
T3058 2733-2735 IN denotes in
T3059 2736-2739 DT denotes the
T3060 2740-2748 NN denotes presence
T3061 2749-2751 IN denotes of
T3062 2752-2753 DT denotes a
T3063 2754-2762 NN denotes cassette
T3064 2763-2773 VBG denotes containing
T3065 2774-2775 DT denotes a
T3066 2790-2796 NN denotes allele
T3067 2776-2782 VBN denotes floxed
T3068 2783-2789 JJ denotes mutant
T3069 2805-2808 DT denotes the
T3070 2818-2826 NN denotes sequence
T3071 2809-2817 JJ denotes resident
T3072 2827-2830 CC denotes and
T3073 2831-2838 VBZ denotes inserts
T3074 2839-2842 DT denotes the
T3075 2850-2854 NN denotes gene
T3076 2843-2849 JJ denotes mutant
T3077 2855-2856 -LRB- denotes (
T3078 2856-2857 CD denotes 7
T3079 2857-2858 -RRB- denotes )
T3080 2858-2859 . denotes .
T3081 2859-2968 sentence denotes Previously, technical difficulties have prevented RMCE from being applied routinely to generate mutant mice.
T3082 2860-2870 RB denotes Previously
T3083 2900-2909 VBN denotes prevented
T3084 2870-2872 , denotes ,
T3085 2872-2881 JJ denotes technical
T3086 2882-2894 NNS denotes difficulties
T3087 2895-2899 VBD denotes have
T3088 2910-2914 NN denotes RMCE
T3089 2915-2919 IN denotes from
T3090 2920-2925 VBG denotes being
T3091 2926-2933 VBN denotes applied
T3092 2934-2943 RB denotes routinely
T3093 2944-2946 TO denotes to
T3094 2947-2955 VB denotes generate
T3095 2956-2962 JJ denotes mutant
T3096 2963-2967 NNS denotes mice
T3097 2967-2968 . denotes .
T3098 2968-3114 sentence denotes For example, exchanges using cassettes with directly repeated loxP sites were inefficient because excisions dominated the intended exchanges (8).
T3099 2969-2972 IN denotes For
T3100 3042-3046 VBD denotes were
T3101 2973-2980 NN denotes example
T3102 2980-2982 , denotes ,
T3103 2982-2991 NNS denotes exchanges
T3104 2992-2997 VBG denotes using
T3105 2998-3007 NNS denotes cassettes
T3106 3008-3012 IN denotes with
T3107 3013-3021 RB denotes directly
T3108 3022-3030 VBN denotes repeated
T3109 3036-3041 NNS denotes sites
T3110 3031-3035 NN denotes loxP
T3111 3047-3058 JJ denotes inefficient
T3112 3059-3066 IN denotes because
T3113 3077-3086 VBD denotes dominated
T3114 3067-3076 NNS denotes excisions
T3115 3087-3090 DT denotes the
T3116 3100-3109 NNS denotes exchanges
T3117 3091-3099 VBN denotes intended
T3118 3110-3111 -LRB- denotes (
T3119 3111-3112 CD denotes 8
T3120 3112-3113 -RRB- denotes )
T3121 3113-3114 . denotes .
T3122 3114-3382 sentence denotes loxP sites with different sequences were generated to overcome this problem, but these sites also underwent intramolecular recombination, making RMCE efficient only if the replacement cassette contained a marker enabling selection of the desired recombinant (7,9–12).
T3123 3115-3119 NN denotes loxP
T3124 3120-3125 NNS denotes sites
T3125 3156-3165 VBN denotes generated
T3126 3126-3130 IN denotes with
T3127 3131-3140 JJ denotes different
T3128 3141-3150 NNS denotes sequences
T3129 3151-3155 VBD denotes were
T3130 3166-3168 TO denotes to
T3131 3169-3177 VB denotes overcome
T3132 3178-3182 DT denotes this
T3133 3183-3190 NN denotes problem
T3134 3190-3192 , denotes ,
T3135 3192-3195 CC denotes but
T3136 3196-3201 DT denotes these
T3137 3202-3207 NNS denotes sites
T3138 3213-3222 VBD denotes underwent
T3139 3208-3212 RB denotes also
T3140 3223-3237 JJ denotes intramolecular
T3141 3238-3251 NN denotes recombination
T3142 3251-3253 , denotes ,
T3143 3253-3259 VBG denotes making
T3144 3260-3264 NN denotes RMCE
T3145 3265-3274 JJ denotes efficient
T3146 3275-3279 RB denotes only
T3147 3308-3317 VBD denotes contained
T3148 3280-3282 IN denotes if
T3149 3283-3286 DT denotes the
T3150 3299-3307 NN denotes cassette
T3151 3287-3298 NN denotes replacement
T3152 3318-3319 DT denotes a
T3153 3320-3326 NN denotes marker
T3154 3327-3335 VBG denotes enabling
T3155 3336-3345 NN denotes selection
T3156 3346-3348 IN denotes of
T3157 3349-3352 DT denotes the
T3158 3361-3372 JJ denotes recombinant
T3159 3353-3360 VBN denotes desired
T3160 3373-3374 -LRB- denotes (
T3161 3374-3375 CD denotes 7
T3162 3375-3376 , denotes ,
T3163 3376-3377 CD denotes 9
T3164 3377-3378 SYM denotes –
T3165 3378-3380 CD denotes 12
T3166 3380-3381 -RRB- denotes )
T3167 3381-3382 . denotes .
T3168 3382-3538 sentence denotes However, interference resulting from expression of the selection marker and the endogenous gene (13) necessitates strategies to remove the selectable gene.
T3169 3383-3390 RB denotes However
T3170 3484-3496 VBZ denotes necessitates
T3171 3390-3392 , denotes ,
T3172 3392-3404 NN denotes interference
T3173 3405-3414 VBG denotes resulting
T3174 3415-3419 IN denotes from
T3175 3420-3430 NN denotes expression
T3176 3431-3433 IN denotes of
T3177 3434-3437 DT denotes the
T3178 3448-3454 NN denotes marker
T3179 3438-3447 NN denotes selection
T3180 3455-3458 CC denotes and
T3181 3459-3462 DT denotes the
T3182 3474-3478 NN denotes gene
T3183 3463-3473 JJ denotes endogenous
T3184 3479-3480 -LRB- denotes (
T3185 3480-3482 CD denotes 13
T3186 3482-3483 -RRB- denotes )
T3187 3497-3507 NNS denotes strategies
T3188 3508-3510 TO denotes to
T3189 3511-3517 VB denotes remove
T3190 3518-3521 DT denotes the
T3191 3533-3537 NN denotes gene
T3192 3522-3532 JJ denotes selectable
T3193 3537-3538 . denotes .
T3194 3538-3882 sentence denotes Together, previous studies indicate that an optimal RMCE requires (i) inverted heterologous loxP sites diverging by at least 2 nt to maximize the efficiency of exchange and (ii) an expression cassette enabling both positive selection to identify the initial recombinant and then negative selection to obtain a ‘marker-free’ mutant allele (14).
T3195 3539-3547 RB denotes Together
T3196 3566-3574 VBP denotes indicate
T3197 3547-3549 , denotes ,
T3198 3549-3557 JJ denotes previous
T3199 3558-3565 NNS denotes studies
T3200 3575-3579 IN denotes that
T3201 3596-3604 VBZ denotes requires
T3202 3580-3582 DT denotes an
T3203 3591-3595 NN denotes RMCE
T3204 3583-3590 JJ denotes optimal
T3205 3605-3606 -LRB- denotes (
T3206 3606-3607 LS denotes i
T3207 3636-3641 NNS denotes sites
T3208 3607-3608 -RRB- denotes )
T3209 3609-3617 VBN denotes inverted
T3210 3618-3630 JJ denotes heterologous
T3211 3631-3635 NN denotes loxP
T3212 3642-3651 VBG denotes diverging
T3213 3652-3654 IN denotes by
T3214 3655-3657 RB denotes at
T3215 3664-3665 CD denotes 2
T3216 3658-3663 RBS denotes least
T3217 3666-3668 NN denotes nt
T3218 3669-3671 TO denotes to
T3219 3672-3680 VB denotes maximize
T3220 3681-3684 DT denotes the
T3221 3685-3695 NN denotes efficiency
T3222 3696-3698 IN denotes of
T3223 3699-3707 NN denotes exchange
T3224 3708-3711 CC denotes and
T3225 3712-3713 -LRB- denotes (
T3226 3713-3715 LS denotes ii
T3227 3731-3739 NN denotes cassette
T3228 3715-3716 -RRB- denotes )
T3229 3717-3719 DT denotes an
T3230 3720-3730 NN denotes expression
T3231 3740-3748 VBG denotes enabling
T3232 3749-3753 CC denotes both
T3233 3763-3772 NN denotes selection
T3234 3754-3762 JJ denotes positive
T3235 3773-3775 TO denotes to
T3236 3776-3784 VB denotes identify
T3237 3785-3788 DT denotes the
T3238 3797-3808 JJ denotes recombinant
T3239 3789-3796 JJ denotes initial
T3240 3809-3812 CC denotes and
T3241 3813-3817 RB denotes then
T3242 3827-3836 NN denotes selection
T3243 3818-3826 JJ denotes negative
T3244 3837-3839 TO denotes to
T3245 3840-3846 VB denotes obtain
T3246 3847-3848 DT denotes a
T3247 3870-3876 NN denotes allele
T3248 3849-3850 `` denotes ‘
T3249 3857-3861 JJ denotes free
T3250 3850-3856 NN denotes marker
T3251 3856-3857 HYPH denotes -
T3252 3861-3862 '' denotes ’
T3253 3863-3869 JJ denotes mutant
T3254 3877-3878 -LRB- denotes (
T3255 3878-3880 CD denotes 14
T3256 3880-3881 -RRB- denotes )
T3257 3881-3882 . denotes .
T3258 3882-3963 sentence denotes Most RMCE experiments have been performed at random sites in somatic cell lines.
T3259 3883-3887 JJS denotes Most
T3260 3893-3904 NNS denotes experiments
T3261 3888-3892 NN denotes RMCE
T3262 3915-3924 VBN denotes performed
T3263 3905-3909 VBP denotes have
T3264 3910-3914 VBN denotes been
T3265 3925-3927 IN denotes at
T3266 3928-3934 JJ denotes random
T3267 3935-3940 NNS denotes sites
T3268 3941-3943 IN denotes in
T3269 3944-3951 JJ denotes somatic
T3270 3952-3956 NN denotes cell
T3271 3957-3962 NNS denotes lines
T3272 3962-3963 . denotes .
T3273 3963-4173 sentence denotes Only a few mutant mice generated by RMCE in ES cells have been reported, but the RMCE systematically introduced a selectable marker (15–17), or, when tested without an incoming marker, proved inefficient (12).
T3274 3964-3968 RB denotes Only
T3275 3982-3986 NNS denotes mice
T3276 3969-3970 DT denotes a
T3277 3971-3974 JJ denotes few
T3278 3975-3981 JJ denotes mutant
T3279 4027-4035 VBN denotes reported
T3280 3987-3996 VBN denotes generated
T3281 3997-3999 IN denotes by
T3282 4000-4004 NN denotes RMCE
T3283 4005-4007 IN denotes in
T3284 4008-4010 NN denotes ES
T3285 4011-4016 NNS denotes cells
T3286 4017-4021 VBP denotes have
T3287 4022-4026 VBN denotes been
T3288 4035-4037 , denotes ,
T3289 4037-4040 CC denotes but
T3290 4041-4044 DT denotes the
T3291 4045-4049 NN denotes RMCE
T3292 4065-4075 VBD denotes introduced
T3293 4050-4064 RB denotes systematically
T3294 4076-4077 DT denotes a
T3295 4089-4095 NN denotes marker
T3296 4078-4088 JJ denotes selectable
T3297 4096-4097 -LRB- denotes (
T3298 4097-4102 CD denotes 15–17
T3299 4102-4103 -RRB- denotes )
T3300 4103-4105 , denotes ,
T3301 4105-4107 CC denotes or
T3302 4107-4109 , denotes ,
T3303 4109-4113 WRB denotes when
T3304 4114-4120 VBN denotes tested
T3305 4149-4155 VBD denotes proved
T3306 4121-4128 IN denotes without
T3307 4129-4131 DT denotes an
T3308 4141-4147 NN denotes marker
T3309 4132-4140 JJ denotes incoming
T3310 4147-4149 , denotes ,
T3311 4156-4167 JJ denotes inefficient
T3312 4168-4169 -LRB- denotes (
T3313 4169-4171 CD denotes 12
T3314 4171-4172 -RRB- denotes )
T3315 4172-4173 . denotes .
T3316 4173-4221 sentence denotes A recent report disclosed an additional problem
T3317 4174-4175 DT denotes A
T3318 4183-4189 NN denotes report
T3319 4176-4182 JJ denotes recent
T3320 4190-4199 VBD denotes disclosed
T3321 4200-4202 DT denotes an
T3322 4214-4221 NN denotes problem
T3323 4203-4213 JJ denotes additional
T3324 4221-4223 : denotes :
T3325 4329-4334 VBZ denotes leads
T3326 4221-4412 sentence denotes : the Hygromycin–Thymidine Kinase fusion gene used most frequently for positive/negative selection in RMCE, leads to mouse sterility, so that exchanges can only be performed in ES cells (16).
T3327 4223-4226 DT denotes the
T3328 4262-4266 NN denotes gene
T3329 4227-4237 NN denotes Hygromycin
T3330 4238-4247 NN denotes Thymidine
T3331 4237-4238 HYPH denotes –
T3332 4248-4254 NN denotes Kinase
T3333 4255-4261 NN denotes fusion
T3334 4267-4271 VBN denotes used
T3335 4272-4276 RBS denotes most
T3336 4277-4287 RB denotes frequently
T3337 4288-4291 IN denotes for
T3338 4292-4300 JJ denotes positive
T3339 4301-4309 JJ denotes negative
T3340 4300-4301 HYPH denotes /
T3341 4310-4319 NN denotes selection
T3342 4320-4322 IN denotes in
T3343 4323-4327 NN denotes RMCE
T3344 4327-4329 , denotes ,
T3345 4335-4337 IN denotes to
T3346 4338-4343 NN denotes mouse
T3347 4344-4353 NN denotes sterility
T3348 4353-4355 , denotes ,
T3349 4355-4357 IN denotes so
T3350 4385-4394 VBN denotes performed
T3351 4358-4362 IN denotes that
T3352 4363-4372 NNS denotes exchanges
T3353 4373-4376 MD denotes can
T3354 4377-4381 RB denotes only
T3355 4382-4384 VB denotes be
T3356 4395-4397 IN denotes in
T3357 4398-4400 NN denotes ES
T3358 4401-4406 NNS denotes cells
T3359 4407-4408 -LRB- denotes (
T3360 4408-4410 CD denotes 16
T3361 4410-4411 -RRB- denotes )
T3362 4411-4412 . denotes .
T3363 4412-4663 sentence denotes The RMCE strategy presented here relies on the integrated use of inverted heterologous loxP sites, a positive/negative selection marker that preserves the germline capacity of ES cells, and the power of mouse genetics to expedite phenotypic analyses.
T3364 4413-4416 DT denotes The
T3365 4422-4430 NN denotes strategy
T3366 4417-4421 NN denotes RMCE
T3367 4446-4452 VBZ denotes relies
T3368 4431-4440 VBN denotes presented
T3369 4441-4445 RB denotes here
T3370 4453-4455 IN denotes on
T3371 4456-4459 DT denotes the
T3372 4471-4474 NN denotes use
T3373 4460-4470 VBN denotes integrated
T3374 4475-4477 IN denotes of
T3375 4478-4486 VBN denotes inverted
T3376 4505-4510 NNS denotes sites
T3377 4487-4499 JJ denotes heterologous
T3378 4500-4504 NN denotes loxP
T3379 4510-4512 , denotes ,
T3380 4512-4513 DT denotes a
T3381 4542-4548 NN denotes marker
T3382 4514-4522 JJ denotes positive
T3383 4523-4531 JJ denotes negative
T3384 4522-4523 HYPH denotes /
T3385 4532-4541 NN denotes selection
T3386 4549-4553 WDT denotes that
T3387 4554-4563 VBZ denotes preserves
T3388 4564-4567 DT denotes the
T3389 4577-4585 NN denotes capacity
T3390 4568-4576 NN denotes germline
T3391 4586-4588 IN denotes of
T3392 4589-4591 NN denotes ES
T3393 4592-4597 NNS denotes cells
T3394 4597-4599 , denotes ,
T3395 4599-4602 CC denotes and
T3396 4603-4606 DT denotes the
T3397 4607-4612 NN denotes power
T3398 4613-4615 IN denotes of
T3399 4616-4621 NN denotes mouse
T3400 4622-4630 NN denotes genetics
T3401 4631-4633 TO denotes to
T3402 4634-4642 VB denotes expedite
T3403 4643-4653 JJ denotes phenotypic
T3404 4654-4662 NNS denotes analyses
T3405 4662-4663 . denotes .
T3406 4663-4897 sentence denotes We show that our approach enables efficient targeting of marker-free mutations at the p53 locus in ES cells to generate mutant mice, but more importantly, it is Adapted for targeting in Somatic cells to Accelerate Phenotyping (ASAP).
T3407 4664-4666 PRP denotes We
T3408 4667-4671 VBP denotes show
T3409 4672-4676 IN denotes that
T3410 4690-4697 VBZ denotes enables
T3411 4677-4680 PRP$ denotes our
T3412 4681-4689 NN denotes approach
T3413 4698-4707 JJ denotes efficient
T3414 4708-4717 NN denotes targeting
T3415 4718-4720 IN denotes of
T3416 4721-4727 JJ denotes marker
T3417 4728-4732 JJ denotes free
T3418 4727-4728 HYPH denotes -
T3419 4733-4742 NNS denotes mutations
T3420 4743-4745 IN denotes at
T3421 4746-4749 DT denotes the
T3422 4754-4759 NN denotes locus
T3423 4750-4753 NN denotes p53
T3424 4760-4762 IN denotes in
T3425 4763-4765 NN denotes ES
T3426 4766-4771 NNS denotes cells
T3427 4772-4774 TO denotes to
T3428 4775-4783 VB denotes generate
T3429 4784-4790 JJ denotes mutant
T3430 4791-4795 NNS denotes mice
T3431 4795-4797 , denotes ,
T3432 4797-4800 CC denotes but
T3433 4801-4805 RBR denotes more
T3434 4806-4817 RB denotes importantly
T3435 4825-4832 VBN denotes Adapted
T3436 4817-4819 , denotes ,
T3437 4819-4821 PRP denotes it
T3438 4822-4824 VBZ denotes is
T3439 4833-4836 IN denotes for
T3440 4837-4846 VBG denotes targeting
T3441 4847-4849 IN denotes in
T3442 4850-4857 JJ denotes Somatic
T3443 4858-4863 NNS denotes cells
T3444 4864-4866 TO denotes to
T3445 4867-4877 VB denotes Accelerate
T3446 4878-4889 NN denotes Phenotyping
T3447 4890-4891 -LRB- denotes (
T3448 4891-4895 NN denotes ASAP
T3449 4895-4896 -RRB- denotes )
T3450 4896-4897 . denotes .
T3451 4897-4996 sentence denotes Because it relies on very general principles, RMCE-ASAP could be applied to any locus of interest.
T3452 4898-4905 IN denotes Because
T3453 4909-4915 VBZ denotes relies
T3454 4906-4908 PRP denotes it
T3455 4963-4970 VBN denotes applied
T3456 4916-4918 IN denotes on
T3457 4919-4923 RB denotes very
T3458 4932-4942 NNS denotes principles
T3459 4924-4931 JJ denotes general
T3460 4942-4944 , denotes ,
T3461 4944-4948 NN denotes RMCE
T3462 4949-4953 NN denotes ASAP
T3463 4948-4949 HYPH denotes -
T3464 4954-4959 MD denotes could
T3465 4960-4962 VB denotes be
T3466 4971-4973 IN denotes to
T3467 4974-4977 DT denotes any
T3468 4978-4983 NN denotes locus
T3469 4984-4986 IN denotes of
T3470 4987-4995 NN denotes interest
T3471 4995-4996 . denotes .
R204 T2571 T2572 nsubj p53,is
R205 T2573 T2572 attr one,is
R206 T2574 T2573 prep of,one
R207 T2575 T2576 det the,proteins
R208 T2576 T2574 pobj proteins,of
R209 T2577 T2578 advmod most,highly
R210 T2578 T2579 advmod highly,analyzed
R211 T2579 T2576 amod analyzed,proteins
R212 T2580 T2572 prep for,is
R213 T2581 T2582 det the,years
R214 T2582 T2580 pobj years,for
R215 T2583 T2582 amod past,years
R216 T2584 T2582 nummod 25,years
R217 T2585 T2572 punct .,is
R218 T2587 T2588 nsubj Studies,established
R219 T2589 T2587 prep in,Studies
R220 T2590 T2591 amod cultured,cells
R221 T2591 T2589 pobj cells,in
R222 T2592 T2587 punct ", ",Studies
R223 T2593 T2594 advmod often,relying
R224 T2594 T2587 acl relying,Studies
R225 T2595 T2594 prep on,relying
R226 T2596 T2597 det the,transfection
R227 T2597 T2595 pobj transfection,on
R228 T2598 T2597 prep of,transfection
R229 T2599 T2598 pobj plasmids,of
R230 T2600 T2599 acl expressing,plasmids
R231 T2601 T2602 amod various,mutants
R232 T2602 T2600 dobj mutants,expressing
R233 T2603 T2602 compound p53,mutants
R234 T2604 T2588 punct ", ",established
R235 T2605 T2588 aux have,established
R236 T2606 T2588 dobj models,established
R237 T2607 T2608 aux to,explain
R238 T2608 T2606 advcl explain,models
R239 T2609 T2610 advmod how,regulated
R240 T2610 T2608 ccomp regulated,explain
R241 T2611 T2610 nsubjpass p53,regulated
R242 T2612 T2610 auxpass is,regulated
R243 T2613 T2588 punct .,established
R244 T2615 T2616 prep In,tested
R245 T2617 T2618 amod recent,years
R246 T2618 T2615 pobj years,In
R247 T2619 T2616 punct ", ",tested
R248 T2620 T2616 nsubjpass some,tested
R249 T2621 T2620 prep of,some
R250 T2622 T2623 det these,models
R251 T2623 T2621 pobj models,of
R252 T2624 T2616 auxpass were,tested
R253 T2625 T2626 advmod in,vivo
R254 T2626 T2616 advmod vivo,tested
R255 T2627 T2616 prep by,tested
R256 T2628 T2627 pcomp targeting,by
R257 T2629 T2630 amod subtle,mutations
R258 T2630 T2628 dobj mutations,targeting
R259 T2631 T2628 prep at,targeting
R260 T2632 T2633 det the,locus
R261 T2633 T2631 pobj locus,at
R262 T2695 T2690 advmod vivo,from
R263 T2634 T2633 compound p53,locus
R264 T2696 T2689 cc and,phenotypes
R265 T2635 T2628 advcl using,targeting
R266 T2697 T2698 compound transfection,data
R267 T2698 T2689 conj data,phenotypes
R268 T2636 T2637 amod homologous,recombination
R269 T2699 T2685 auxpass were,observed
R270 T2637 T2635 dobj recombination,using
R271 T2701 T2702 punct [,1
R272 T2702 T2685 parataxis 1,observed
R273 T2703 T2702 advmod e.g.,1
R274 T2638 T2635 prep in,using
R275 T2704 T2702 nmod Refs,1
R276 T2705 T2702 punct (,1
R277 T2639 T2640 amod embryonic,stem
R278 T2706 T2707 punct –,5
R279 T2707 T2702 prep 5,1
R280 T2708 T2702 punct ),1
R281 T2640 T2641 nmod stem,cells
R282 T2709 T2702 punct ],1
R283 T2641 T2638 pobj cells,in
R284 T2710 T2700 punct ", ",need
R285 T2642 T2640 punct (,stem
R286 T2711 T2712 advmod more,targeted
R287 T2712 T2713 amod targeted,mutations
R288 T2643 T2640 appos ES,stem
R289 T2713 T2700 nsubj mutations,need
R290 T2714 T2715 aux to,generated
R291 T2715 T2700 xcomp generated,need
R292 T2716 T2715 auxpass be,generated
R293 T2644 T2641 punct ),cells
R294 T2717 T2715 cc and,generated
R295 T2718 T2715 conj analyzed,generated
R296 T2645 T2646 aux to,generate
R297 T2719 T2718 prep in,analyzed
R298 T2720 T2721 amod multiple,tissues
R299 T2721 T2719 pobj tissues,in
R300 T2722 T2723 aux to,formulate
R301 T2723 T2718 advcl formulate,analyzed
R302 T2724 T2725 advmod more,accurate
R303 T2646 T2635 advcl generate,using
R304 T2725 T2726 amod accurate,models
R305 T2647 T2648 amod mutant,mice
R306 T2726 T2723 dobj models,formulate
R307 T2727 T2726 prep of,models
R308 T2728 T2729 compound p53,regulation
R309 T2729 T2727 pobj regulation,of
R310 T2730 T2700 punct .,need
R311 T2648 T2646 dobj mice,generate
R312 T2732 T2733 advmod However,is
R313 T2649 T2616 punct .,tested
R314 T2734 T2733 punct ", ",is
R315 T2735 T2733 csubj using,is
R316 T2651 T2652 det The,strength
R317 T2736 T2737 amod homologous,recombination
R318 T2652 T2653 nsubj strength,is
R319 T2737 T2735 dobj recombination,using
R320 T2738 T2735 prep in,using
R321 T2654 T2652 prep of,strength
R322 T2739 T2740 compound ES,cells
R323 T2740 T2738 pobj cells,in
R324 T2741 T2742 aux to,generate
R325 T2655 T2656 det this,approach
R326 T2742 T2735 advcl generate,using
R327 T2743 T2744 amod mutant,mice
R328 T2744 T2742 dobj mice,generate
R329 T2745 T2746 det an,method
R330 T2656 T2654 pobj approach,of
R331 T2746 T2733 attr method,is
R332 T2747 T2746 amod inefficient,method
R333 T2748 T2747 punct ", ",inefficient
R334 T2657 T2658 mark that,tested
R335 T2749 T2747 conj slow,inefficient
R336 T2750 T2749 cc and,slow
R337 T2658 T2653 ccomp tested,is
R338 T2751 T2749 conj expensive,slow
R339 T2752 T2753 mark because,occurs
R340 T2753 T2733 advcl occurs,is
R341 T2659 T2658 nsubj mutations,tested
R342 T2754 T2755 punct (,i
R343 T2755 T2753 meta i,occurs
R344 T2756 T2755 punct ),i
R345 T2757 T2758 amod homologous,recombination
R346 T2660 T2658 aux are,tested
R347 T2758 T2753 nsubj recombination,occurs
R348 T2759 T2753 advmod typically,occurs
R349 T2760 T2753 prep at,occurs
R350 T2661 T2658 prep in,tested
R351 T2761 T2762 amod low,frequency
R352 T2762 T2760 pobj frequency,at
R353 T2763 T2753 prep in,occurs
R354 T2764 T2765 compound ES,cells
R355 T2765 T2763 pobj cells,in
R356 T2766 T2753 punct ", ",occurs
R357 T2662 T2663 det a,setting
R358 T2767 T2753 advcl requiring,occurs
R359 T2768 T2769 amod sophisticated,schemes
R360 T2663 T2661 pobj setting,in
R361 T2769 T2767 dobj schemes,requiring
R362 T2770 T2769 compound selection,schemes
R363 T2771 T2769 cc and,schemes
R364 T2772 T2769 conj screening,schemes
R365 T2664 T2663 amod genomic,setting
R366 T2773 T2772 prep of,screening
R367 T2774 T2773 pobj hundreds,of
R368 T2665 T2658 cc and,tested
R369 T2775 T2774 prep of,hundreds
R370 T2776 T2775 pobj clones,of
R371 T2777 T2778 aux to,identify
R372 T2666 T2658 conj expressed,tested
R373 T2778 T2767 advcl identify,requiring
R374 T2779 T2780 det the,mutant
R375 T2780 T2778 dobj mutant,identify
R376 T2667 T2666 prep from,expressed
R377 T2781 T2780 amod desired,mutant
R378 T2782 T2753 punct ;,occurs
R379 T2783 T2784 punct (,ii
R380 T2668 T2669 det the,promoter
R381 T2784 T2785 meta ii,plasmids
R382 T2669 T2667 pobj promoter,from
R383 T2785 T2794 nsubjpass plasmids,required
R384 T2786 T2784 punct ),ii
R385 T2670 T2669 amod endogenous,promoter
R386 T2787 T2785 amod large,plasmids
R387 T2788 T2789 punct (,kb
R388 T2789 T2785 parataxis kb,plasmids
R389 T2790 T2791 quantmod 15,20
R390 T2671 T2658 punct ", ",tested
R391 T2791 T2789 nummod 20,kb
R392 T2792 T2791 punct –,20
R393 T2793 T2789 punct ),kb
R394 T2672 T2658 advcl ensuring,tested
R395 T2794 T2753 conj required,occurs
R396 T2795 T2785 punct ", ",plasmids
R397 T2796 T2797 advmod often,difficult
R398 T2673 T2674 amod physiological,levels
R399 T2797 T2785 amod difficult,plasmids
R400 T2798 T2799 aux to,clone
R401 T2674 T2672 dobj levels,ensuring
R402 T2799 T2797 advcl clone,difficult
R403 T2800 T2794 punct ", ",required
R404 T2675 T2674 compound expression,levels
R405 T2676 T2674 cc and,levels
R406 T2801 T2794 auxpass are,required
R407 T2677 T2678 amod correct,profiles
R408 T2802 T2803 aux to,increase
R409 T2803 T2794 advcl increase,required
R410 T2678 T2674 conj profiles,levels
R411 T2804 T2805 amod targeting,efficiency
R412 T2805 T2803 dobj efficiency,increase
R413 T2806 T2794 cc and,required
R414 T2679 T2680 amod spatio,temporal
R415 T2807 T2808 punct (,iii
R416 T2808 T2809 meta iii,generate
R417 T2680 T2678 amod temporal,profiles
R418 T2809 T2794 conj generate,required
R421 T2681 T2680 punct -,temporal
R422 T2812 T2811 dobj mice,breeding
R423 T2813 T2811 prep to,breeding
R424 T2814 T2813 pobj homozygosity,to
R425 T2682 T2653 punct .,is
R426 T2815 T2811 cc and,breeding
R427 T2816 T2811 conj housing,breeding
R428 T2684 T2685 mark As,observed
R429 T2817 T2818 det a,colony
R430 T2818 T2816 dobj colony,housing
R431 T2819 T2818 compound mouse,colony
R432 T2820 T2821 amod further,delays
R433 T2821 T2809 dobj delays,generate
R434 T2685 T2700 advcl observed,need
R435 T2822 T2821 cc and,delays
R436 T2823 T2821 conj costs,delays
R437 T2824 T2733 punct .,is
R438 T2686 T2687 amod significant,differences
R439 T2826 T2827 amod Such,limitations
R440 T2687 T2685 nsubjpass differences,observed
R441 T2827 T2828 nsubj limitations,make
R442 T2829 T2830 det the,targeting
R443 T2688 T2687 prep between,differences
R444 T2830 T2832 nsubj targeting,task
R445 T2831 T2830 amod repeated,targeting
R446 T2832 T2828 ccomp task,make
R447 T2689 T2688 pobj phenotypes,between
R448 T2833 T2830 prep of,targeting
R449 T2834 T2835 det a,locus
R450 T2835 T2833 pobj locus,of
R451 T2690 T2689 prep from,phenotypes
R452 T2836 T2832 det a,task
R453 T2837 T2838 advmod technically,daunting
R454 T2838 T2832 amod daunting,task
R455 T2691 T2692 amod targeted,mutants
R456 T2839 T2838 cc and,daunting
R457 T2840 T2841 advmod economically,impractical
R458 T2841 T2838 conj impractical,daunting
R459 T2842 T2828 punct .,make
R460 T2844 T2845 nsubjpass Improvements,needed
R461 T2692 T2690 pobj mutants,from
R462 T2846 T2844 prep in,Improvements
R463 T2693 T2692 compound p53,mutants
R464 T2847 T2848 amod current,technologies
R465 T2848 T2846 pobj technologies,in
R466 T2849 T2845 auxpass are,needed
R467 T2694 T2695 advmod in,vivo
R468 T2850 T2851 aux to,enable
R469 T2851 T2845 advcl enable,needed
R470 T2907 T2905 compound read,out
R471 T2852 T2853 amod such,analyses
R472 T2853 T2851 dobj analyses,enable
R473 T2854 T2855 aux to,applied
R474 T2855 T2851 xcomp applied,enable
R475 T2908 T2905 punct -,out
R476 T2856 T2855 auxpass be,applied
R477 T2857 T2855 dative to,applied
R478 T2858 T2859 det the,p53
R479 T2909 T2905 prep than,out
R480 T2859 T2857 pobj p53,to
R481 T2860 T2859 cc or,p53
R482 T2910 T2911 amod equivalent,outs
R483 T2861 T2862 amod other,genes
R484 T2862 T2859 conj genes,p53
R485 T2863 T2845 punct .,needed
R486 T2911 T2909 pobj outs,than
R487 T2865 T2866 csubj Developing,is
R488 T2912 T2911 compound gene,outs
R489 T2867 T2865 dobj methods,Developing
R490 T2868 T2869 aux to,increase
R491 T2913 T2911 compound knock,outs
R492 T2869 T2867 advcl increase,methods
R493 T2870 T2871 amod targeting,efficiency
R494 T2871 T2869 dobj efficiency,increase
R495 T2872 T2869 prep in,increase
R496 T2914 T2911 punct -,outs
R497 T2873 T2874 compound ES,cells
R498 T2874 T2872 pobj cells,in
R499 T2915 T2911 prep in,outs
R500 T2875 T2866 advmod clearly,is
R501 T2876 T2877 det an,goal
R502 T2877 T2866 attr goal,is
R503 T2916 T2915 pobj animals,in
R504 T2878 T2877 amod important,goal
R505 T2917 T2918 punct (,6
R506 T2879 T2866 punct .,is
R507 T2918 T2898 parataxis 6,provide
R508 T2881 T2882 prep In,expedite
R509 T2883 T2881 pobj addition,In
R510 T2884 T2882 punct ", ",expedite
R511 T2885 T2886 amod efficient,methods
R512 T2919 T2918 punct ),6
R513 T2886 T2882 nsubj methods,expedite
R514 T2887 T2886 prep for,methods
R515 T2888 T2889 compound gene,targeting
R516 T2920 T2898 punct .,provide
R517 T2889 T2887 pobj targeting,for
R518 T2890 T2889 prep in,targeting
R519 T2922 T2923 advmod However,requires
R520 T2891 T2890 pobj fibroblasts,in
R521 T2892 T2882 aux could,expedite
R523 T2893 T2894 amod phenotypic,analyses
R524 T2894 T2882 dobj analyses,expedite
R525 T2895 T2882 punct .,expedite
R526 T2897 T2898 advmod Indeed,provide
R527 T2925 T2923 csubj modeling,requires
R528 T2899 T2898 punct ", ",provide
R529 T2926 T2927 advmod most,mutations
R530 T2900 T2898 nsubj siRNAs,provide
R531 T2901 T2900 prep in,siRNAs
R532 T2902 T2901 pobj fibroblasts,in
R533 T2927 T2925 dobj mutations,modeling
R534 T2903 T2898 advmod often,provide
R535 T2904 T2905 det a,out
R536 T2905 T2898 dobj out,provide
R537 T2906 T2905 amod faster,out
R538 T2928 T2929 npadvmod disease,associated
R539 T2929 T2927 amod associated,mutations
R540 T2930 T2929 punct -,associated
R541 T2931 T2923 xcomp generating,requires
R542 T2932 T2933 amod subtle,mutations
R543 T3013 T3011 dobj process,using
R544 T2933 T2931 dobj mutations,generating
R545 T3014 T3015 nummod two,step
R546 T3015 T3013 compound step,process
R547 T3016 T3015 punct -,step
R548 T2934 T2933 punct ", ",mutations
R549 T3017 T3006 punct : ,replaced
R550 T3018 T3019 det the,gene
R551 T2935 T2933 cc not,mutations
R552 T3019 T3006 nsubjpass gene,replaced
R553 T3020 T3019 prep of,gene
R554 T3021 T3020 pobj interest,of
R555 T2936 T2937 compound knock,outs
R556 T3022 T3006 auxpass is,replaced
R557 T3023 T3006 advmod first,replaced
R558 T3024 T3006 agent by,replaced
R559 T2937 T2933 conj outs,mutations
R560 T3025 T3026 det a,cassette
R561 T3026 T3024 pobj cassette,by
R562 T3027 T3026 compound selection,cassette
R563 T3028 T3026 acl flanked,cassette
R564 T3029 T3028 agent by,flanked
R565 T3030 T3031 compound recombinase,sites
R566 T2938 T2937 punct -,outs
R567 T3031 T3029 pobj sites,by
R568 T3032 T3031 compound target,sites
R569 T3033 T3034 punct (,sites
R570 T2939 T2937 cc or,outs
R571 T3034 T3031 parataxis sites,sites
R572 T3035 T3034 advmod e.g.,sites
R573 T3036 T3034 compound loxP,sites
R574 T2940 T2941 amod reduced,expression
R575 T3037 T3034 prep for,sites
R576 T3038 T3039 compound Cre,recombinase
R577 T3039 T3037 pobj recombinase,for
R578 T2941 T2942 compound expression,alleles
R579 T3040 T3034 punct ", ",sites
R580 T2942 T2937 conj alleles,outs
R581 T3041 T3042 aux to,create
R582 T3042 T3034 advcl create,sites
R583 T2943 T2923 punct .,requires
R584 T3043 T3044 det a,locus
R585 T3044 T3042 dobj locus,create
R586 T3045 T3044 punct ‘,locus
R587 T2945 T2946 csubj Targeting,is
R588 T3046 T3044 amod floxed,locus
R589 T3047 T3044 punct ’,locus
R590 T3048 T3034 punct ),sites
R591 T3049 T3006 punct .,replaced
R592 T2947 T2948 compound point,mutations
R593 T3051 T3052 advmod Then,removes
R594 T3053 T3052 punct ", ",removes
R595 T2948 T2945 dobj mutations,Targeting
R596 T2949 T2945 prep in,Targeting
R597 T3054 T3055 npadvmod Cre,mediated
R598 T3055 T3057 amod mediated,recombination
R599 T3056 T3055 punct -,mediated
R600 T2950 T2949 pobj fibroblasts,in
R601 T3057 T3052 nsubj recombination,removes
R602 T3058 T3057 prep in,recombination
R603 T3059 T3060 det the,presence
R604 T2951 T2945 prep by,Targeting
R605 T3060 T3058 pobj presence,in
R606 T3061 T3060 prep of,presence
R607 T3062 T3063 det a,cassette
R608 T2952 T2953 amod homologous,recombination
R609 T3063 T3061 pobj cassette,of
R610 T3064 T3063 acl containing,cassette
R611 T2953 T2951 pobj recombination,by
R612 T3065 T3066 det a,allele
R613 T3066 T3064 dobj allele,containing
R614 T3067 T3066 amod floxed,allele
R615 T3068 T3066 amod mutant,allele
R616 T3069 T3070 det the,sequence
R617 T3070 T3052 dobj sequence,removes
R618 T2954 T2955 advmod extremely,inefficient
R619 T3071 T3070 amod resident,sequence
R620 T3072 T3052 cc and,removes
R621 T3073 T3052 conj inserts,removes
R622 T3074 T3075 det the,gene
R623 T2955 T2946 acomp inefficient,is
R624 T3075 T3073 dobj gene,inserts
R625 T3076 T3075 amod mutant,gene
R626 T3077 T3078 punct (,7
R627 T2956 T2946 punct ", ",is
R628 T3078 T3073 parataxis 7,inserts
R629 T3079 T3078 punct ),7
R630 T3080 T3052 punct .,removes
R631 T2957 T2946 cc and,is
R632 T3082 T3083 advmod Previously,prevented
R633 T2958 T2959 csubjpass targeting,required
R634 T2959 T2946 conj required,is
R635 T3084 T3083 punct ", ",prevented
R636 T3085 T3086 amod technical,difficulties
R637 T3086 T3083 nsubj difficulties,prevented
R638 T3087 T3083 aux have,prevented
R639 T2960 T2961 det both,alleles
R640 T3088 T3083 dobj RMCE,prevented
R641 T3089 T3083 prep from,prevented
R642 T3090 T3091 auxpass being,applied
R643 T2961 T2958 dobj alleles,targeting
R644 T3091 T3089 pcomp applied,from
R645 T3092 T3091 advmod routinely,applied
R646 T3093 T3094 aux to,generate
R647 T2962 T2959 auxpass is,required
R648 T3094 T3091 advcl generate,applied
R649 T3095 T3096 amod mutant,mice
R650 T3096 T3094 dobj mice,generate
R651 T2963 T2964 aux to,reveal
R652 T3097 T3083 punct .,prevented
R653 T2964 T2959 advcl reveal,required
R654 T3099 T3100 prep For,were
R655 T3101 T3099 pobj example,For
R656 T2965 T2966 det the,phenotype
R657 T3102 T3100 punct ", ",were
R658 T3103 T3100 nsubj exchanges,were
R659 T3104 T3103 acl using,exchanges
R660 T2966 T2964 dobj phenotype,reveal
R661 T3105 T3104 dobj cassettes,using
R662 T3106 T3104 prep with,using
R663 T3107 T3108 advmod directly,repeated
R664 T2967 T2966 prep of,phenotype
R665 T3108 T3109 amod repeated,sites
R666 T3109 T3106 pobj sites,with
R667 T3110 T3109 compound loxP,sites
R668 T3111 T3100 acomp inefficient,were
R669 T3112 T3113 mark because,dominated
R670 T3113 T3100 advcl dominated,were
R671 T2968 T2969 amod recessive,autosomal
R672 T3114 T3113 nsubj excisions,dominated
R673 T3115 T3116 det the,exchanges
R674 T3116 T3113 dobj exchanges,dominated
R675 T2969 T2970 amod autosomal,mutations
R676 T3117 T3116 amod intended,exchanges
R677 T3118 T3119 punct (,8
R678 T2970 T2967 pobj mutations,of
R679 T2971 T2959 punct .,required
R680 T3119 T3113 parataxis 8,dominated
R681 T2973 T2974 advmod Here,report
R682 T3120 T3119 punct ),8
R683 T3121 T3100 punct .,were
R684 T3123 T3124 compound loxP,sites
R685 T2975 T2974 nsubj we,report
R686 T3124 T3125 nsubjpass sites,generated
R687 T3126 T3124 prep with,sites
R688 T2976 T2977 det an,approach
R689 T3127 T3128 amod different,sequences
R690 T3128 T3126 pobj sequences,with
R691 T2977 T2974 dobj approach,report
R692 T3129 T3125 auxpass were,generated
R693 T3130 T3131 aux to,overcome
R694 T2978 T2979 dep that,enables
R695 T3131 T3125 advcl overcome,generated
R696 T3132 T3133 det this,problem
R697 T3133 T3131 dobj problem,overcome
R698 T2979 T2977 relcl enables,approach
R699 T3134 T3125 punct ", ",generated
R700 T3135 T3125 cc but,generated
R701 T3136 T3137 det these,sites
R702 T2980 T2981 advmod highly,efficient
R703 T3137 T3138 nsubj sites,underwent
R704 T3138 T3125 conj underwent,generated
R705 T3139 T3138 advmod also,underwent
R706 T2981 T2982 amod efficient,targeting
R707 T2982 T2979 dobj targeting,enables
R708 T3140 T3141 amod intramolecular,recombination
R709 T3141 T3138 dobj recombination,underwent
R710 T2983 T2979 prep at,enables
R711 T3142 T3138 punct ", ",underwent
R712 T3143 T3138 advcl making,underwent
R713 T2984 T2985 det the,locus
R714 T3144 T3145 nsubj RMCE,efficient
R715 T3145 T3143 ccomp efficient,making
R716 T3146 T3147 advmod only,contained
R717 T3147 T3143 advcl contained,making
R718 T3148 T3147 mark if,contained
R719 T2985 T2983 pobj locus,at
R720 T3149 T3150 det the,cassette
R721 T3150 T3147 nsubj cassette,contained
R722 T3151 T3150 compound replacement,cassette
R723 T3152 T3153 det a,marker
R724 T2986 T2985 compound p53,locus
R725 T3153 T3147 dobj marker,contained
R726 T3154 T3153 acl enabling,marker
R727 T2987 T2979 prep in,enables
R728 T3155 T3154 dobj selection,enabling
R729 T3156 T3155 prep of,selection
R730 T3157 T3158 det the,recombinant
R731 T3158 T3156 pobj recombinant,of
R732 T2988 T2989 preconj both,cells
R733 T3159 T3158 amod desired,recombinant
R734 T3160 T3161 punct (,7
R735 T2989 T2987 pobj cells,in
R736 T3161 T3147 parataxis 7,contained
R737 T3162 T3161 punct ",",7
R738 T3163 T3161 appos 9,7
R739 T2990 T2989 compound ES,cells
R740 T3164 T3165 punct –,12
R741 T3165 T3163 prep 12,9
R742 T2991 T2989 cc and,cells
R743 T3166 T3161 punct ),7
R744 T3167 T3138 punct .,underwent
R745 T2992 T2989 conj fibroblasts,cells
R746 T3169 T3170 advmod However,necessitates
R747 T3171 T3170 punct ", ",necessitates
R748 T3172 T3170 nsubj interference,necessitates
R749 T2993 T2974 punct .,report
R750 T3173 T3172 acl resulting,interference
R751 T3174 T3173 prep from,resulting
R752 T2995 T2996 npadvmod Recombinase,Mediated
R753 T3175 T3174 pobj expression,from
R754 T3176 T3175 prep of,expression
R755 T3177 T3178 det the,marker
R756 T3178 T3176 pobj marker,of
R757 T2996 T2998 amod Mediated,Exchange
R758 T3179 T3178 compound selection,marker
R759 T3180 T3178 cc and,marker
R760 T3181 T3182 det the,gene
R761 T2997 T2996 punct -,Mediated
R762 T3182 T3178 conj gene,marker
R763 T3183 T3182 amod endogenous,gene
R764 T3184 T3185 punct (,13
R765 T2998 T3000 nmod Exchange,approaches
R766 T3185 T3173 parataxis 13,resulting
R767 T3186 T3185 punct ),13
R768 T3187 T3170 dobj strategies,necessitates
R769 T3188 T3189 aux to,remove
R770 T3189 T3187 advcl remove,strategies
R771 T3190 T3191 det the,gene
R772 T3191 T3189 dobj gene,remove
R773 T2999 T2998 nmod Cassette,Exchange
R774 T3192 T3191 amod selectable,gene
R776 T3000 T3004 nsubjpass approaches,developed
R777 T3195 T3196 advmod Together,indicate
R778 T3197 T3196 punct ", ",indicate
R779 T3001 T2998 punct (,Exchange
R780 T3198 T3199 amod previous,studies
R781 T3199 T3196 nsubj studies,indicate
R782 T3200 T3201 mark that,requires
R783 T3002 T2998 appos RMCE,Exchange
R785 T3202 T3203 det an,RMCE
R786 T3003 T3000 punct ),approaches
R787 T3203 T3201 nsubj RMCE,requires
R788 T3204 T3203 amod optimal,RMCE
R789 T3205 T3206 punct (,i
R790 T3004 T3006 ccomp developed,replaced
R791 T3206 T3207 meta i,sites
R792 T3207 T3201 dobj sites,requires
R793 T3208 T3206 punct ),i
R794 T3005 T3004 auxpass were,developed
R795 T3209 T3207 amod inverted,sites
R796 T3007 T3008 aux to,improve
R797 T3210 T3207 amod heterologous,sites
R798 T3211 T3207 compound loxP,sites
R799 T3212 T3207 acl diverging,sites
R800 T3213 T3212 prep by,diverging
R801 T3214 T3215 quantmod at,2
R802 T3215 T3217 nummod 2,nt
R803 T3008 T3004 advcl improve,developed
R804 T3216 T3214 advmod least,at
R805 T3217 T3213 pobj nt,by
R806 T3218 T3219 aux to,maximize
R807 T3009 T3010 amod targeting,efficiency
R808 T3219 T3207 advcl maximize,sites
R809 T3220 T3221 det the,efficiency
R810 T3221 T3219 dobj efficiency,maximize
R811 T3010 T3008 dobj efficiency,improve
R812 T3222 T3221 prep of,efficiency
R813 T3223 T3222 pobj exchange,of
R814 T3011 T3008 advcl using,improve
R815 T3012 T3013 det a,process
R816 T3224 T3207 cc and,sites
R817 T3331 T3330 punct –,Thymidine
R818 T3332 T3328 compound Kinase,gene
R819 T3225 T3226 punct (,ii
R820 T3226 T3227 meta ii,cassette
R821 T3333 T3328 compound fusion,gene
R822 T3227 T3207 conj cassette,sites
R823 T3228 T3226 punct ),ii
R824 T3229 T3227 det an,cassette
R825 T3230 T3227 compound expression,cassette
R826 T3231 T3227 acl enabling,cassette
R827 T3232 T3233 preconj both,selection
R828 T3334 T3328 acl used,gene
R829 T3233 T3231 dobj selection,enabling
R830 T3234 T3233 amod positive,selection
R831 T3335 T3336 advmod most,frequently
R832 T3235 T3236 aux to,identify
R833 T3236 T3231 advcl identify,enabling
R834 T3237 T3238 det the,recombinant
R835 T3336 T3334 advmod frequently,used
R836 T3238 T3236 dobj recombinant,identify
R837 T3239 T3238 amod initial,recombinant
R838 T3240 T3231 cc and,enabling
R839 T3337 T3334 prep for,used
R840 T3241 T3242 advmod then,selection
R841 T3242 T3231 conj selection,enabling
R842 T3243 T3242 amod negative,selection
R843 T3244 T3245 aux to,obtain
R844 T3338 T3339 amod positive,negative
R845 T3245 T3242 advcl obtain,selection
R846 T3246 T3247 det a,allele
R847 T3247 T3245 dobj allele,obtain
R848 T3339 T3341 nmod negative,selection
R849 T3248 T3249 punct ‘,free
R850 T3249 T3247 amod free,allele
R851 T3340 T3339 punct /,negative
R852 T3250 T3249 npadvmod marker,free
R853 T3251 T3249 punct -,free
R854 T3252 T3249 punct ’,free
R855 T3341 T3337 pobj selection,for
R856 T3253 T3247 amod mutant,allele
R857 T3254 T3255 punct (,14
R858 T3255 T3242 parataxis 14,selection
R859 T3342 T3341 prep in,selection
R860 T3256 T3255 punct ),14
R861 T3257 T3196 punct .,indicate
R862 T3343 T3342 pobj RMCE,in
R863 T3259 T3260 amod Most,experiments
R864 T3260 T3262 nsubjpass experiments,performed
R865 T3261 T3260 compound RMCE,experiments
R866 T3344 T3325 punct ", ",leads
R867 T3263 T3262 aux have,performed
R868 T3264 T3262 auxpass been,performed
R869 T3345 T3325 prep to,leads
R870 T3265 T3262 prep at,performed
R871 T3266 T3267 amod random,sites
R872 T3267 T3265 pobj sites,at
R873 T3346 T3347 compound mouse,sterility
R874 T3268 T3267 prep in,sites
R875 T3269 T3270 amod somatic,cell
R876 T3270 T3271 compound cell,lines
R877 T3271 T3268 pobj lines,in
R878 T3272 T3262 punct .,performed
R879 T3347 T3345 pobj sterility,to
R880 T3274 T3275 advmod Only,mice
R881 T3275 T3279 nsubjpass mice,reported
R882 T3276 T3275 det a,mice
R883 T3348 T3325 punct ", ",leads
R884 T3277 T3275 amod few,mice
R885 T3278 T3275 amod mutant,mice
R886 T3349 T3350 mark so,performed
R887 T3280 T3275 acl generated,mice
R888 T3281 T3280 agent by,generated
R889 T3282 T3281 pobj RMCE,by
R890 T3350 T3325 advcl performed,leads
R891 T3283 T3282 prep in,RMCE
R892 T3284 T3285 compound ES,cells
R893 T3351 T3350 mark that,performed
R894 T3285 T3283 pobj cells,in
R895 T3286 T3279 aux have,reported
R896 T3287 T3279 auxpass been,reported
R897 T3288 T3279 punct ", ",reported
R898 T3352 T3350 nsubjpass exchanges,performed
R899 T3289 T3279 cc but,reported
R900 T3290 T3291 det the,RMCE
R901 T3353 T3350 aux can,performed
R902 T3291 T3292 nsubj RMCE,introduced
R903 T3292 T3279 conj introduced,reported
R904 T3354 T3350 advmod only,performed
R905 T3293 T3292 advmod systematically,introduced
R906 T3294 T3295 det a,marker
R907 T3295 T3292 dobj marker,introduced
R908 T3296 T3295 amod selectable,marker
R909 T3355 T3350 auxpass be,performed
R910 T3297 T3298 punct (,15–17
R911 T3298 T3292 parataxis 15–17,introduced
R912 T3299 T3298 punct ),15–17
R913 T3356 T3350 prep in,performed
R914 T3300 T3292 punct ", ",introduced
R915 T3301 T3292 cc or,introduced
R916 T3357 T3358 compound ES,cells
R917 T3302 T3292 punct ", ",introduced
R918 T3303 T3304 advmod when,tested
R919 T3358 T3356 pobj cells,in
R920 T3304 T3305 advcl tested,proved
R921 T3359 T3360 punct (,16
R922 T3305 T3292 conj proved,introduced
R923 T3360 T3325 parataxis 16,leads
R924 T3306 T3304 prep without,tested
R925 T3307 T3308 det an,marker
R926 T3308 T3306 pobj marker,without
R927 T3309 T3308 amod incoming,marker
R928 T3310 T3305 punct ", ",proved
R929 T3311 T3305 oprd inefficient,proved
R930 T3312 T3313 punct (,12
R931 T3361 T3360 punct ),16
R932 T3313 T3305 parataxis 12,proved
R933 T3314 T3313 punct ),12
R934 T3315 T3292 punct .,introduced
R935 T3362 T3325 punct .,leads
R936 T3317 T3318 det A,report
R937 T3364 T3365 det The,strategy
R938 T3318 T3320 nsubj report,disclosed
R939 T3319 T3318 amod recent,report
R940 T3321 T3322 det an,problem
R941 T3365 T3367 nsubj strategy,relies
R942 T3322 T3320 dobj problem,disclosed
R943 T3323 T3322 amod additional,problem
R944 T3324 T3325 punct : ,leads
R945 T3366 T3365 compound RMCE,strategy
R946 T3327 T3328 det the,gene
R947 T3368 T3365 acl presented,strategy
R948 T3328 T3325 nsubj gene,leads
R949 T3329 T3330 compound Hygromycin,Thymidine
R950 T3330 T3332 compound Thymidine,Kinase
R951 T3369 T3368 advmod here,presented
R952 T3370 T3367 prep on,relies
R953 T3371 T3372 det the,use
R954 T3372 T3370 pobj use,on
R955 T3437 T3435 nsubjpass it,Adapted
R956 T3373 T3372 amod integrated,use
R957 T3438 T3435 auxpass is,Adapted
R958 T3439 T3435 prep for,Adapted
R959 T3374 T3372 prep of,use
R960 T3440 T3439 pobj targeting,for
R961 T3375 T3376 amod inverted,sites
R962 T3441 T3440 prep in,targeting
R963 T3442 T3443 amod Somatic,cells
R964 T3443 T3441 pobj cells,in
R965 T3376 T3374 pobj sites,of
R966 T3444 T3445 aux to,Accelerate
R967 T3445 T3435 advcl Accelerate,Adapted
R968 T3377 T3376 amod heterologous,sites
R969 T3446 T3445 dobj Phenotyping,Accelerate
R970 T3447 T3446 punct (,Phenotyping
R971 T3448 T3446 appos ASAP,Phenotyping
R972 T3449 T3435 punct ),Adapted
R973 T3378 T3376 compound loxP,sites
R974 T3450 T3435 punct .,Adapted
R975 T3379 T3372 punct ", ",use
R976 T3452 T3453 mark Because,relies
R977 T3453 T3455 advcl relies,applied
R978 T3454 T3453 nsubj it,relies
R979 T3456 T3453 prep on,relies
R980 T3457 T3458 advmod very,principles
R981 T3380 T3381 det a,marker
R982 T3458 T3456 pobj principles,on
R983 T3459 T3458 amod general,principles
R984 T3460 T3455 punct ", ",applied
R985 T3381 T3372 conj marker,use
R986 T3461 T3462 compound RMCE,ASAP
R987 T3462 T3455 nsubjpass ASAP,applied
R988 T3463 T3462 punct -,ASAP
R989 T3382 T3383 amod positive,negative
R990 T3464 T3455 aux could,applied
R991 T3465 T3455 auxpass be,applied
R992 T3466 T3455 prep to,applied
R993 T3383 T3385 nmod negative,selection
R994 T3467 T3468 det any,locus
R995 T3468 T3466 pobj locus,to
R996 T3469 T3468 prep of,locus
R997 T3384 T3383 punct /,negative
R998 T3470 T3469 pobj interest,of
R999 T3471 T3455 punct .,applied
R1000 T3385 T3381 compound selection,marker
R1001 T3386 T3387 dep that,preserves
R1002 T3387 T3381 relcl preserves,marker
R1003 T3388 T3389 det the,capacity
R1004 T3389 T3387 dobj capacity,preserves
R1005 T3390 T3389 compound germline,capacity
R1006 T3391 T3389 prep of,capacity
R1007 T3392 T3393 compound ES,cells
R1008 T3393 T3391 pobj cells,of
R1009 T3394 T3381 punct ", ",marker
R1010 T3395 T3381 cc and,marker
R1011 T3396 T3397 det the,power
R1012 T3397 T3381 conj power,marker
R1013 T3398 T3397 prep of,power
R1014 T3399 T3400 compound mouse,genetics
R1015 T3400 T3398 pobj genetics,of
R1016 T3401 T3402 aux to,expedite
R1017 T3402 T3367 advcl expedite,relies
R1018 T3403 T3404 amod phenotypic,analyses
R1019 T3404 T3402 dobj analyses,expedite
R1020 T3405 T3367 punct .,relies
R1021 T3407 T3408 nsubj We,show
R1022 T3409 T3410 mark that,enables
R1023 T3410 T3408 ccomp enables,show
R1024 T3411 T3412 poss our,approach
R1025 T3412 T3410 nsubj approach,enables
R1026 T3413 T3414 amod efficient,targeting
R1027 T3414 T3410 dobj targeting,enables
R1028 T3415 T3414 prep of,targeting
R1029 T3416 T3417 amod marker,free
R1030 T3417 T3419 amod free,mutations
R1031 T3418 T3417 punct -,free
R1032 T3419 T3415 pobj mutations,of
R1033 T3420 T3419 prep at,mutations
R1034 T3421 T3422 det the,locus
R1035 T3422 T3420 pobj locus,at
R1036 T3423 T3422 compound p53,locus
R1037 T3424 T3414 prep in,targeting
R1038 T3425 T3426 compound ES,cells
R1039 T3426 T3424 pobj cells,in
R1040 T3427 T3428 aux to,generate
R1041 T3428 T3410 xcomp generate,enables
R1042 T3429 T3430 amod mutant,mice
R1043 T3430 T3428 dobj mice,generate
R1044 T3431 T3408 punct ", ",show
R1045 T3432 T3408 cc but,show
R1046 T3433 T3434 advmod more,importantly
R1047 T3434 T3435 advmod importantly,Adapted
R1048 T3435 T3408 conj Adapted,show
R1049 T3436 T3435 punct ", ",Adapted
R419 T2810 T2808 punct ),iii
R420 T2811 T2809 csubj breeding,generate
R522 T2924 T2923 punct ", ",requires
R775 T3193 T3170 punct .,necessitates
R784 T3201 T3196 ccomp requires,indicate

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
T2414 13-16 PR_EXT:000003035 denotes p53
T2415 52-60 CHEBI_PR_EXT:protein denotes proteins
T2417 104-109 CL_GO_EXT:cell denotes cells
T2418 132-144 GO:0009294 denotes transfection
T2419 148-156 SO_EXT:0000155 denotes plasmids
T2420 157-167 GO:0010467 denotes expressing
T2421 176-179 PR_EXT:000003035 denotes p53
T2422 180-187 SO_EXT:sequence_altered_entity denotes mutants
T2423 228-231 PR_EXT:000003035 denotes p53
T2424 235-244 GO:0065007 denotes regulated
T2425 324-333 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2426 341-344 PR_EXT:000003035 denotes p53
T2427 368-381 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T2428 385-394 UBERON:0000922 denotes embryonic
T2429 385-399 _FRAGMENT denotes embryonic stem
T2430 405-410 CL:0002322 denotes cells
T2431 401-403 _FRAGMENT denotes ES
T2432 405-410 CL_GO_EXT:cell denotes cells
T2433 423-429 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2434 430-434 NCBITaxon:10088 denotes mice
T2435 474-483 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2436 500-507 SO_EXT:0001026 denotes genomic
T2437 520-529 GO:0010467 denotes expressed
T2438 550-558 SO_EXT:0000167 denotes promoter
T2439 569-582 GO_PATO_EXT:physiological_process_or_quality denotes physiological
T2440 583-593 GO:0010467 denotes expression
T2441 699-702 PR_EXT:000003035 denotes p53
T2442 703-710 SO_EXT:sequence_altered_entity denotes mutants
T2443 723-735 GO:0009294 denotes transfection
T2444 788-797 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2445 889-892 PR_EXT:000003035 denotes p53
T2446 893-903 GO:0065007 denotes regulation
T2447 931-944 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T2448 948-956 CL:0002322 denotes ES cells
T2449 951-956 CL_GO_EXT:cell denotes cells
T2450 969-975 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2451 976-980 NCBITaxon:10088 denotes mice
T2452 1049-1062 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T2453 1100-1108 CL:0002322 denotes ES cells
T2454 1103-1108 CL_GO_EXT:cell denotes cells
T2455 1181-1187 SO_EXT:sequence_cloned_entity denotes clones
T2456 1212-1218 SO_EXT:sequence_altered_entity denotes mutant
T2457 1239-1240 CHEBI_SO_EXT:base denotes b
T2458 1242-1250 SO_EXT:0000155 denotes plasmids
T2459 1271-1276 SO_EXT:sequence_cloning_process denotes clone
T2460 1334-1342 GO_EXT:breeding denotes breeding
T2461 1343-1347 NCBITaxon:10088 denotes mice
T2462 1378-1383 NCBITaxon:10088 denotes mouse
T2463 1633-1636 PR_EXT:000003035 denotes p53
T2464 1646-1651 SO_EXT:0000704 denotes genes
T2465 1708-1716 CL:0002322 denotes ES cells
T2466 1711-1716 CL_GO_EXT:cell denotes cells
T2467 1782-1786 SO_EXT:0000704 denotes gene
T2468 1800-1811 CL:0000057 denotes fibroblasts
T2469 1856-1862 SO_EXT:0000646 denotes siRNAs
T2470 1866-1877 CL:0000057 denotes fibroblasts
T2471 1926-1930 SO_EXT:0000704 denotes gene
T2472 1945-1952 NCBITaxon:33208 denotes animals
T2473 2000-2009 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2474 2037-2046 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2475 2074-2084 GO:0010467 denotes expression
T2476 2085-2092 SO_EXT:0001023 denotes alleles
T2477 2104-2119 SO_EXT:point_mutation_entity_or_process denotes point mutations
T2478 2123-2134 CL:0000057 denotes fibroblasts
T2479 2149-2162 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T2480 2208-2215 SO_EXT:0001023 denotes alleles
T2481 2265-2274 GO:0030849 denotes autosomal
T2482 2275-2284 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2483 2360-2363 PR_EXT:000003035 denotes p53
T2484 2378-2386 CL:0002322 denotes ES cells
T2485 2381-2386 CL_GO_EXT:cell denotes cells
T2486 2391-2402 CL:0000057 denotes fibroblasts
T2487 2404-2415 GO_EXT:recombinase denotes Recombinase
T2488 2425-2433 SO_EXT:0005853 denotes Cassette
T2489 2434-2442 SO_EXT:sequence_substitution_process denotes Exchange
T2490 2538-2542 SO_EXT:0000704 denotes gene
T2491 2564-2572 SO_EXT:sequence_substitution_process denotes replaced
T2492 2588-2596 SO_EXT:0005853 denotes cassette
T2493 2597-2604 SO:0000357 denotes flanked
T2494 2608-2619 GO_EXT:recombinase denotes recombinase
T2495 2639-2649 SO_EXT:0000346 denotes loxP sites
T2496 2658-2669 GO_EXT:recombinase denotes recombinase
T2497 2684-2690 SO:0000359 denotes floxed
T2498 2719-2732 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T2499 2754-2762 SO_EXT:0005853 denotes cassette
T2500 2776-2782 SO:0000359 denotes floxed
T2501 2783-2789 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2502 2790-2796 SO_EXT:0001023 denotes allele
T2503 2818-2826 SO_EXT:biological_sequence denotes sequence
T2504 2831-2838 SO_EXT:sequence_insertion_process denotes inserts
T2505 2843-2849 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2506 2850-2854 SO_EXT:0000704 denotes gene
T2507 2956-2962 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2508 2963-2967 NCBITaxon:10088 denotes mice
T2509 2982-2991 SO_EXT:sequence_substitution_process denotes exchanges
T2510 2998-3007 SO_EXT:0005853 denotes cassettes
T2511 3022-3030 SO_EXT:sequence_repeat_unit_or_region denotes repeated
T2512 3031-3041 SO_EXT:0000346 denotes loxP sites
T2513 3067-3076 SO_EXT:sequence_deletion_process denotes excisions
T2514 3100-3109 SO_EXT:sequence_substitution_process denotes exchanges
T2515 3115-3125 SO_EXT:0000346 denotes loxP sites
T2516 3141-3150 SO_EXT:biological_sequence denotes sequences
T2517 3228-3237 CHEBI_EXT:polyatomic_entity_or_group denotes molecular
T2518 3238-3251 GO_SO_EXT:sequence_rearrangement_process denotes recombination
T2519 3287-3298 SO_EXT:sequence_substitution_entity_or_process denotes replacement
T2520 3299-3307 SO_EXT:0005853 denotes cassette
T2521 3320-3326 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes marker
T2522 3361-3372 SO_EXT:sequence_recombinant_entity denotes recombinant
T2523 3420-3430 GO:0010467 denotes expression
T2524 3448-3454 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes marker
T2525 3474-3478 SO_EXT:0000704 denotes gene
T2526 3533-3537 SO_EXT:0000704 denotes gene
T2527 3609-3617 _FRAGMENT denotes inverted
T2528 3636-3641 SO_EXT:0000948 denotes sites
T2529 3631-3641 SO_EXT:0000346 denotes loxP sites
T2530 3666-3668 CHEBI_SO_EXT:nucleotide denotes nt
T2531 3699-3707 SO_EXT:sequence_substitution_process denotes exchange
T2532 3720-3730 GO:0010467 denotes expression
T2533 3731-3739 SO_EXT:0005853 denotes cassette
T2534 3797-3808 SO_EXT:sequence_recombinant_entity denotes recombinant
T2535 3850-3856 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes marker
T2536 3863-3869 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2537 3870-3876 SO_EXT:0001023 denotes allele
T2538 3944-3956 CL:0002371 denotes somatic cell
T2539 3952-3956 CL_GO_EXT:cell denotes cell
T2540 3975-3981 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2541 3982-3986 NCBITaxon:10088 denotes mice
T2542 4008-4016 CL:0002322 denotes ES cells
T2543 4011-4016 CL_GO_EXT:cell denotes cells
T2544 4089-4095 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes marker
T2545 4141-4147 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes marker
T2546 4227-4237 CHEBI:24753 denotes Hygromycin
T2547 4238-4247 CHEBI_EXT:thymine_nucleobase_or_nucleoside_or_nucleotide_molecular_entity_or_group denotes Thymidine
T2548 4238-4254 GO_PR_EXT:thymidine_kinase denotes Thymidine Kinase
T2549 4255-4266 SO_EXT:fusion_gene_or_gene_fusion denotes fusion gene
T2550 4338-4343 NCBITaxon:10088 denotes mouse
T2551 4363-4372 SO_EXT:sequence_substitution_process denotes exchanges
T2552 4398-4406 CL:0002322 denotes ES cells
T2553 4401-4406 CL_GO_EXT:cell denotes cells
T2554 4478-4486 _FRAGMENT denotes inverted
T2555 4505-4510 SO_EXT:0000948 denotes sites
T2556 4500-4510 SO_EXT:0000346 denotes loxP sites
T2557 4542-4548 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes marker
T2558 4589-4597 CL:0002322 denotes ES cells
T2559 4592-4597 CL_GO_EXT:cell denotes cells
T2560 4616-4621 NCBITaxon:10088 denotes mouse
T2561 4622-4630 OBI_SO_EXT:gene_or_genetic_investigation_or_genetic_process denotes genetics
T2562 4721-4727 CHEBI_SO_EXT:molecular_indicator_or_label_or_marker_or_tag denotes marker
T2563 4733-4742 SO_EXT:sequence_alteration_entity_or_process denotes mutations
T2564 4750-4753 PR_EXT:000003035 denotes p53
T2565 4763-4771 CL:0002322 denotes ES cells
T2566 4766-4771 CL_GO_EXT:cell denotes cells
T2567 4784-4790 SO_EXT:sequence_altered_entity_or_alteration_process denotes mutant
T2568 4791-4795 NCBITaxon:10088 denotes mice
T2569 4850-4863 CL:0002371 denotes Somatic cells
T2570 4858-4863 CL_GO_EXT:cell denotes cells
T2416 95-109 CL:0000010 denotes cultured cells
R200 T2430 T2429 _lexicallyChainedTo cells,embryonic stem
R201 T2430 T2431 _lexicallyChainedTo cells,ES
R202 T2528 T2527 _lexicallyChainedTo sites,inverted
R203 T2555 T2554 _lexicallyChainedTo sites,inverted

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
T2330 13-16 PR:000003035 denotes p53
T2331 95-109 CL:0000010 denotes cultured cells
T2332 132-144 GO:0009294 denotes transfection
T2333 148-156 SO:0000155 denotes plasmids
T2334 157-167 GO:0010467 denotes expressing
T2335 176-179 PR:000003035 denotes p53
T2336 228-231 PR:000003035 denotes p53
T2337 235-244 GO:0065007 denotes regulated
T2338 341-344 PR:000003035 denotes p53
T2339 385-394 UBERON:0000922 denotes embryonic
T2340 385-399 _FRAGMENT denotes embryonic stem
T2341 405-410 CL:0002322 denotes cells
T2342 401-403 _FRAGMENT denotes ES
T2343 430-434 NCBITaxon:10088 denotes mice
T2344 500-507 SO:0001026 denotes genomic
T2345 520-529 GO:0010467 denotes expressed
T2346 550-558 SO:0000167 denotes promoter
T2347 583-593 GO:0010467 denotes expression
T2348 699-702 PR:000003035 denotes p53
T2349 723-735 GO:0009294 denotes transfection
T2350 889-892 PR:000003035 denotes p53
T2351 893-903 GO:0065007 denotes regulation
T2352 948-956 CL:0002322 denotes ES cells
T2353 976-980 NCBITaxon:10088 denotes mice
T2354 1100-1108 CL:0002322 denotes ES cells
T2355 1242-1250 SO:0000155 denotes plasmids
T2356 1343-1347 NCBITaxon:10088 denotes mice
T2357 1378-1383 NCBITaxon:10088 denotes mouse
T2358 1633-1636 PR:000003035 denotes p53
T2359 1646-1651 SO:0000704 denotes genes
T2360 1708-1716 CL:0002322 denotes ES cells
T2361 1782-1786 SO:0000704 denotes gene
T2362 1800-1811 CL:0000057 denotes fibroblasts
T2363 1856-1862 SO:0000646 denotes siRNAs
T2364 1866-1877 CL:0000057 denotes fibroblasts
T2365 1926-1930 SO:0000704 denotes gene
T2366 1945-1952 NCBITaxon:33208 denotes animals
T2367 2074-2084 GO:0010467 denotes expression
T2368 2085-2092 SO:0001023 denotes alleles
T2369 2123-2134 CL:0000057 denotes fibroblasts
T2370 2208-2215 SO:0001023 denotes alleles
T2371 2265-2274 GO:0030849 denotes autosomal
T2372 2360-2363 PR:000003035 denotes p53
T2373 2378-2386 CL:0002322 denotes ES cells
T2374 2391-2402 CL:0000057 denotes fibroblasts
T2375 2425-2433 SO:0005853 denotes Cassette
T2376 2538-2542 SO:0000704 denotes gene
T2377 2588-2596 SO:0005853 denotes cassette
T2378 2597-2604 SO:0000357 denotes flanked
T2379 2639-2649 SO:0000346 denotes loxP sites
T2380 2684-2690 SO:0000359 denotes floxed
T2381 2754-2762 SO:0005853 denotes cassette
T2382 2776-2782 SO:0000359 denotes floxed
T2383 2790-2796 SO:0001023 denotes allele
T2384 2850-2854 SO:0000704 denotes gene
T2385 2963-2967 NCBITaxon:10088 denotes mice
T2386 2998-3007 SO:0005853 denotes cassettes
T2387 3031-3041 SO:0000346 denotes loxP sites
T2388 3115-3125 SO:0000346 denotes loxP sites
T2389 3299-3307 SO:0005853 denotes cassette
T2390 3420-3430 GO:0010467 denotes expression
T2391 3474-3478 SO:0000704 denotes gene
T2392 3533-3537 SO:0000704 denotes gene
T2393 3609-3617 _FRAGMENT denotes inverted
T2394 3636-3641 SO:0000948 denotes sites
T2395 3631-3641 SO:0000346 denotes loxP sites
T2396 3720-3730 GO:0010467 denotes expression
T2397 3731-3739 SO:0005853 denotes cassette
T2398 3870-3876 SO:0001023 denotes allele
T2399 3944-3956 CL:0002371 denotes somatic cell
T2400 3982-3986 NCBITaxon:10088 denotes mice
T2401 4008-4016 CL:0002322 denotes ES cells
T2402 4227-4237 CHEBI:24753 denotes Hygromycin
T2403 4338-4343 NCBITaxon:10088 denotes mouse
T2404 4398-4406 CL:0002322 denotes ES cells
T2405 4478-4486 _FRAGMENT denotes inverted
T2406 4505-4510 SO:0000948 denotes sites
T2407 4500-4510 SO:0000346 denotes loxP sites
T2408 4589-4597 CL:0002322 denotes ES cells
T2409 4616-4621 NCBITaxon:10088 denotes mouse
T2410 4750-4753 PR:000003035 denotes p53
T2411 4763-4771 CL:0002322 denotes ES cells
T2412 4791-4795 NCBITaxon:10088 denotes mice
T2413 4850-4863 CL:0002371 denotes Somatic cells
R196 T2341 T2340 _lexicallyChainedTo cells,embryonic stem
R197 T2341 T2342 _lexicallyChainedTo cells,ES
R198 T2394 T2393 _lexicallyChainedTo sites,inverted
R199 T2406 T2405 _lexicallyChainedTo sites,inverted

2_test

Id Subject Object Predicate Lexical cue
16870721-12909629-76660890 767-768 12909629 denotes 1
16870721-15456863-76660890 767-768 15456863 denotes 1
16870721-14729946-76660890 767-768 14729946 denotes 1
16870721-16006521-76660890 767-768 16006521 denotes 1
16870721-16616333-76660890 767-768 16616333 denotes 1
16870721-12074888-76660891 1954-1955 12074888 denotes 6
16870721-9345015-76660892 2856-2857 9345015 denotes 7
16870721-2783482-76660893 3111-3112 2783482 denotes 8
16870721-9345015-76660894 3374-3375 9345015 denotes 7
16870721-10525404-76660895 3376-3377 10525404 denotes 9
16870721-11237328-76660895 3376-3377 11237328 denotes 9
16870721-12136089-76660895 3376-3377 12136089 denotes 9
16870721-16028230-76660895 3376-3377 16028230 denotes 9
16870721-11584291-76660896 3480-3482 11584291 denotes 13
16870721-16204450-76660897 3878-3880 16204450 denotes 14
16870721-12563279-76660898 4097-4099 12563279 denotes 15
16870721-14994271-76660898 4097-4099 14994271 denotes 15
16870721-16382151-76660898 4097-4099 16382151 denotes 15
16870721-16028230-76660899 4169-4171 16028230 denotes 12
16870721-14994271-76660900 4408-4410 14994271 denotes 16