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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. Ultimately, breeding pairs were used in which the mice were heterozygous for the LAP-tTA transgene, the TRE-E2 transgene, and the E2 knockout. To efficiently screen for the ability of the transgenes to rescue the knockout from neonatal lethality, we genotyped litters at weaning. 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%. Fig. 4A shows the percentage of mice alive at weaning with the rescue genotype from each transgenic line tested. Considerable variability was observed between lines. The line with the highest percentage of rescue mice at weaning was line 525 A. Approximately 10% of weaned, surviving pups from this line had the rescue genotype. Thus, the 525A transgene appears to be highly effective at rescuing the neonatal lethal phenotype of the E2 knockout. In contrast, line 520B completely failed to rescue the neonatal lethal phenotype. All other lines tested produced surviving rescue animals at a frequency between 1 and 5% of weaned pups."}

{"project":"craft-ca-core-ex-dev","denotations":[{"id":"T15598","span":{"begin":923,"end":927},"obj":"NCBITaxon_UBERON_EXT:pup"},{"id":"T15597","span":{"begin":852,"end":856},"obj":"NCBITaxon:10088"},{"id":"T15596","span":{"begin":845,"end":851},"obj":"SO_EXT:sequence_rescue_process"},{"id":"T15595","span":{"begin":728,"end":738},"obj":"SO_EXT:transgenic_entity"},{"id":"T15594","span":{"begin":709,"end":717},"obj":"SO_EXT:genotype_or_entity_with_genotype"},{"id":"T15593","span":{"begin":702,"end":708},"obj":"SO_EXT:sequence_rescue_process"},{"id":"T15592","span":{"begin":671,"end":675},"obj":"NCBITaxon:10088"},{"id":"T15591","span":{"begin":619,"end":629},"obj":"SO_EXT:0000902"},{"id":"T15590","span":{"begin":585,"end":587},"obj":"PR_EXT:000006300"},{"id":"T15589","span":{"begin":558,"end":566},"obj":"SO_EXT:genotype_or_entity_with_genotype"},{"id":"T15588","span":{"begin":551,"end":557},"obj":"SO_EXT:sequence_rescue_process"},{"id":"T15587","span":{"begin":534,"end":541},"obj":"NCBITaxon:33208"},{"id":"T15586","span":{"begin":466,"end":474},"obj":"GO_EXT:breeding"},{"id":"T15585","span":{"begin":417,"end":426},"obj":"GO_EXT:fatality_or_lethality"},{"id":"T15584","span":{"begin":408,"end":416},"obj":"PATO_UBERON_EXT:neonate_or_newborn"},{"id":"T15583","span":{"begin":383,"end":389},"obj":"SO_EXT:sequence_rescue_process"},{"id":"T15582","span":{"begin":369,"end":379},"obj":"SO_EXT:0000902"},{"id":"T15581","span":{"begin":311,"end":313},"obj":"PR_EXT:000006300"},{"id":"T15580","span":{"begin":292,"end":301},"obj":"SO_EXT:0000902"},{"id":"T15579","span":{"begin":289,"end":291},"obj":"PR_EXT:000006300"},{"id":"T15578","span":{"begin":270,"end":279},"obj":"SO_EXT:0000902"},{"id":"T15577","span":{"begin":262,"end":265},"obj":"PR_EXT:000005308"},{"id":"T15576","span":{"begin":231,"end":235},"obj":"NCBITaxon:10088"},{"id":"T15575","span":{"begin":193,"end":201},"obj":"GO_EXT:breeding"},{"id":"T15574","span":{"begin":168,"end":170},"obj":"PR_EXT:000006300"},{"id":"T15573","span":{"begin":128,"end":137},"obj":"SO_EXT:0000902"},{"id":"T15572","span":{"begin":120,"end":123},"obj":"PR_EXT:000005308"},{"id":"T15571","span":{"begin":88,"end":92},"obj":"NCBITaxon:10088"},{"id":"T15570","span":{"begin":18,"end":22},"obj":"NCBITaxon:10088"},{"id":"T15569","span":{"begin":15,"end":17},"obj":"PR_EXT:000006300"},{"id":"T15568","span":{"begin":0,"end":10},"obj":"SO_EXT:transgenic_entity"},{"id":"T15612","span":{"begin":1267,"end":1271},"obj":"NCBITaxon_UBERON_EXT:pup"},{"id":"T15611","span":{"begin":1217,"end":1224},"obj":"NCBITaxon:33208"},{"id":"T15610","span":{"begin":1210,"end":1216},"obj":"SO_EXT:sequence_rescue_process"},{"id":"T15609","span":{"begin":1150,"end":1156},"obj":"GO_EXT:fatality_or_lethality"},{"id":"T15608","span":{"begin":1141,"end":1149},"obj":"PATO_UBERON_EXT:neonate_or_newborn"},{"id":"T15607","span":{"begin":1130,"end":1136},"obj":"SO_EXT:sequence_rescue_process"},{"id":"T15606","span":{"begin":1073,"end":1075},"obj":"PR_EXT:000006300"},{"id":"T15605","span":{"begin":1049,"end":1055},"obj":"GO_EXT:fatality_or_lethality"},{"id":"T15604","span":{"begin":1040,"end":1048},"obj":"PATO_UBERON_EXT:neonate_or_newborn"},{"id":"T15603","span":{"begin":1027,"end":1035},"obj":"SO_EXT:sequence_rescue_process"},{"id":"T15602","span":{"begin":983,"end":992},"obj":"SO_EXT:0000902"},{"id":"T15601","span":{"begin":958,"end":966},"obj":"SO_EXT:genotype_or_entity_with_genotype"},{"id":"T15600","span":{"begin":951,"end":957},"obj":"SO_EXT:sequence_rescue_process"}],"text":"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. Ultimately, breeding pairs were used in which the mice were heterozygous for the LAP-tTA transgene, the TRE-E2 transgene, and the E2 knockout. To efficiently screen for the ability of the transgenes to rescue the knockout from neonatal lethality, we genotyped litters at weaning. 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%. Fig. 4A shows the percentage of mice alive at weaning with the rescue genotype from each transgenic line tested. Considerable variability was observed between lines. The line with the highest percentage of rescue mice at weaning was line 525 A. Approximately 10% of weaned, surviving pups from this line had the rescue genotype. Thus, the 525A transgene appears to be highly effective at rescuing the neonatal lethal phenotype of the E2 knockout. In contrast, line 520B completely failed to rescue the neonatal lethal phenotype. All other lines tested produced surviving rescue animals at a frequency between 1 and 5% of weaned pups."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T15420","span":{"begin":1217,"end":1224},"obj":"NCBITaxon:33208"},{"id":"T15419","span":{"begin":1073,"end":1075},"obj":"PR:000006300"},{"id":"T15418","span":{"begin":983,"end":992},"obj":"SO:0000902"},{"id":"T15417","span":{"begin":852,"end":856},"obj":"NCBITaxon:10088"},{"id":"T15416","span":{"begin":671,"end":675},"obj":"NCBITaxon:10088"},{"id":"T15415","span":{"begin":619,"end":629},"obj":"SO:0000902"},{"id":"T15414","span":{"begin":585,"end":587},"obj":"PR:000006300"},{"id":"T15413","span":{"begin":534,"end":541},"obj":"NCBITaxon:33208"},{"id":"T15412","span":{"begin":369,"end":379},"obj":"SO:0000902"},{"id":"T15411","span":{"begin":311,"end":313},"obj":"PR:000006300"},{"id":"T15410","span":{"begin":292,"end":301},"obj":"SO:0000902"},{"id":"T15409","span":{"begin":289,"end":291},"obj":"PR:000006300"},{"id":"T15408","span":{"begin":270,"end":279},"obj":"SO:0000902"},{"id":"T15407","span":{"begin":262,"end":265},"obj":"PR:000005308"},{"id":"T15406","span":{"begin":231,"end":235},"obj":"NCBITaxon:10088"},{"id":"T15405","span":{"begin":168,"end":170},"obj":"PR:000006300"},{"id":"T15404","span":{"begin":128,"end":137},"obj":"SO:0000902"},{"id":"T15403","span":{"begin":120,"end":123},"obj":"PR:000005308"},{"id":"T15402","span":{"begin":88,"end":92},"obj":"NCBITaxon:10088"},{"id":"T15401","span":{"begin":18,"end":22},"obj":"NCBITaxon:10088"},{"id":"T15400","span":{"begin":15,"end":17},"obj":"PR:000006300"}],"text":"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. Ultimately, breeding pairs were used in which the mice were heterozygous for the LAP-tTA transgene, the TRE-E2 transgene, and the E2 knockout. To efficiently screen for the ability of the transgenes to rescue the knockout from neonatal lethality, we genotyped litters at weaning. 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%. Fig. 4A shows the percentage of mice alive at weaning with the rescue genotype from each transgenic line tested. Considerable variability was observed between lines. The line with the highest percentage of rescue mice at weaning was line 525 A. Approximately 10% of weaned, surviving pups from this line had the rescue genotype. Thus, the 525A transgene appears to be highly effective at rescuing the neonatal lethal phenotype of the E2 knockout. In contrast, line 520B completely failed to rescue the neonatal lethal phenotype. All other lines tested produced surviving rescue animals at a frequency between 1 and 5% of weaned pups."}