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underlying cause of the preimplantation lethality in Capn2-/- embryos has not yet been clarified. The two homozygous null embryos identified at the 8-cell stage did not present any obvious morphological defects. However, the fact that only two out of 90 successfully genotyped pre-implantation embryos proved to be Capn2-/- is in itself revealing. Preimplantation lethality resulting from gene knockouts can typically be attributed to two general causes. In some cases, defects are incurred in the embryonic differentiation program which can often be observed morphologically [38]. Null embryos of this type often survive beyond the morula stage, and a Mendelian distribution of embryonic genotypes is usually noted. In other cases, however, the gene disruption is thought to compromise fatally the viability of cells in the early embryo [3,39-43]. In these instances, only a few null embryos are ever observed and homozygous mutant ES cells could not be isolated. The Capn2 knockout fits into the latter category. If it is true that m-calpain is essential for some aspect of cell viability, the survival of a few Capn2-/- embryos to the 8-cell stage is most likely due to the persistence of some maternal m-calpain mRNA and/or protein through 2–3 cell divisions."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T12338","span":{"begin":1252,"end":1266},"obj":"GO:0051301"},{"id":"T12337","span":{"begin":1142,"end":1154},"obj":"UBERON:0019252"},{"id":"T12336","span":{"begin":1127,"end":1134},"obj":"UBERON:0000922"},{"id":"T12335","span":{"begin":1118,"end":1123},"obj":"PR:000005015"},{"id":"T12334","span":{"begin":973,"end":978},"obj":"PR:000005015"},{"id":"T12333","span":{"begin":937,"end":945},"obj":"CL:0002322"},{"id":"T12332","span":{"begin":889,"end":896},"obj":"UBERON:0000922"},{"id":"T12331","span":{"begin":829,"end":841},"obj":"UBERON:0019248"},{"id":"T12330","span":{"begin":750,"end":754},"obj":"SO:0000704"},{"id":"T12329","span":{"begin":683,"end":692},"obj":"UBERON:0000922"},{"id":"T12328","span":{"begin":637,"end":643},"obj":"UBERON:0000085"},{"id":"T12327","span":{"begin":591,"end":598},"obj":"UBERON:0000922"},{"id":"T12326","span":{"begin":502,"end":511},"obj":"UBERON:0000922"},{"id":"T12325","span":{"begin":393,"end":397},"obj":"SO:0000704"},{"id":"T12324","span":{"begin":355,"end":367},"obj":"GO:0007566"},{"id":"T12323","span":{"begin":319,"end":324},"obj":"PR:000005015"},{"id":"T12322","span":{"begin":298,"end":305},"obj":"UBERON:0000922"},{"id":"T12321","span":{"begin":285,"end":297},"obj":"GO:0007566"},{"id":"T12320","span":{"begin":152,"end":164},"obj":"UBERON:0019252"},{"id":"T12319","span":{"begin":126,"end":133},"obj":"UBERON:0000922"},{"id":"T12318","span":{"begin":66,"end":73},"obj":"UBERON:0000922"},{"id":"T12317","span":{"begin":57,"end":62},"obj":"PR:000005015"},{"id":"T12316","span":{"begin":31,"end":43},"obj":"GO:0007566"}],"text":"The underlying cause of the preimplantation lethality in Capn2-/- embryos has not yet been clarified. The two homozygous null embryos identified at the 8-cell stage did not present any obvious morphological defects. However, the fact that only two out of 90 successfully genotyped pre-implantation embryos proved to be Capn2-/- is in itself revealing. Preimplantation lethality resulting from gene knockouts can typically be attributed to two general causes. In some cases, defects are incurred in the embryonic differentiation program which can often be observed morphologically [38]. Null embryos of this type often survive beyond the morula stage, and a Mendelian distribution of embryonic genotypes is usually noted. In other cases, however, the gene disruption is thought to compromise fatally the viability of cells in the early embryo [3,39-43]. In these instances, only a few null embryos are ever observed and homozygous mutant ES cells could not be isolated. The Capn2 knockout fits into the latter category. If it is true that m-calpain is essential for some aspect of cell viability, the survival of a few Capn2-/- embryos to the 8-cell stage is most likely due to the persistence of some maternal m-calpain mRNA and/or protein through 2–3 cell divisions."}

{"project":"craft-ca-core-ex-dev","denotations":[{"id":"T12673","span":{"begin":1252,"end":1266},"obj":"GO:0051301"},{"id":"T12672","span":{"begin":1252,"end":1256},"obj":"CL_GO_EXT:cell"},{"id":"T12671","span":{"begin":1232,"end":1239},"obj":"CHEBI_PR_EXT:protein"},{"id":"T12670","span":{"begin":1220,"end":1224},"obj":"CHEBI_SO_EXT:mRNA"},{"id":"T12669","span":{"begin":1210,"end":1219},"obj":"GO_PR_EXT:calpain_2_complex"},{"id":"T12668","span":{"begin":1144,"end":1148},"obj":"CL_GO_EXT:cell"},{"id":"T12667","span":{"begin":1142,"end":1154},"obj":"UBERON:0019252"},{"id":"T12666","span":{"begin":1127,"end":1134},"obj":"UBERON:0000922"},{"id":"T12665","span":{"begin":1125,"end":1126},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T12664","span":{"begin":1123,"end":1124},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T12663","span":{"begin":1118,"end":1123},"obj":"PR_EXT:000005015"},{"id":"T12662","span":{"begin":1080,"end":1084},"obj":"CL_GO_EXT:cell"},{"id":"T12661","span":{"begin":1038,"end":1047},"obj":"GO_PR_EXT:calpain_2_complex"},{"id":"T12660","span":{"begin":973,"end":978},"obj":"PR_EXT:000005015"},{"id":"T12659","span":{"begin":940,"end":945},"obj":"CL_GO_EXT:cell"},{"id":"T12658","span":{"begin":937,"end":945},"obj":"CL:0002322"},{"id":"T12657","span":{"begin":930,"end":936},"obj":"SO_EXT:sequence_altered_entity_or_alteration_process"},{"id":"T12656","span":{"begin":889,"end":896},"obj":"UBERON:0000922"},{"id":"T12655","span":{"begin":884,"end":888},"obj":"SO_EXT:sequence_nullness"},{"id":"T12654","span":{"begin":829,"end":841},"obj":"UBERON:0019248"},{"id":"T12653","span":{"begin":816,"end":821},"obj":"CL_GO_EXT:cell"},{"id":"T12652","span":{"begin":791,"end":798},"obj":"GO_EXT:fatality_or_lethality"},{"id":"T12651","span":{"begin":750,"end":754},"obj":"SO_EXT:0000704"},{"id":"T12650","span":{"begin":693,"end":702},"obj":"SO_EXT:genotype_or_entity_with_genotype"},{"id":"T12649","span":{"begin":683,"end":692},"obj":"UBERON:0000922"},{"id":"T12648","span":{"begin":637,"end":643},"obj":"UBERON:0000085"},{"id":"T12647","span":{"begin":591,"end":598},"obj":"UBERON:0000922"},{"id":"T12646","span":{"begin":586,"end":590},"obj":"SO_EXT:sequence_nullness"},{"id":"T12645","span":{"begin":512,"end":527},"obj":"GO_RO_EXT:developmental_differentiation_process"},{"id":"T12644","span":{"begin":502,"end":511},"obj":"UBERON:0000922"},{"id":"T12643","span":{"begin":393,"end":397},"obj":"SO_EXT:0000704"},{"id":"T12642","span":{"begin":368,"end":377},"obj":"GO_EXT:fatality_or_lethality"},{"id":"T12641","span":{"begin":355,"end":367},"obj":"GO:0007566"},{"id":"T12640","span":{"begin":326,"end":327},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T12639","span":{"begin":324,"end":325},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T12638","span":{"begin":319,"end":324},"obj":"PR_EXT:000005015"},{"id":"T12637","span":{"begin":298,"end":305},"obj":"UBERON:0000922"},{"id":"T12636","span":{"begin":285,"end":297},"obj":"GO:0007566"},{"id":"T12635","span":{"begin":154,"end":158},"obj":"CL_GO_EXT:cell"},{"id":"T12634","span":{"begin":152,"end":164},"obj":"UBERON:0019252"},{"id":"T12633","span":{"begin":126,"end":133},"obj":"UBERON:0000922"},{"id":"T12632","span":{"begin":121,"end":125},"obj":"SO_EXT:sequence_nullness"},{"id":"T12631","span":{"begin":66,"end":73},"obj":"UBERON:0000922"},{"id":"T12630","span":{"begin":64,"end":65},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T12629","span":{"begin":62,"end":63},"obj":"SO_EXT:sequence_nullness_or_absence"},{"id":"T12628","span":{"begin":57,"end":62},"obj":"PR_EXT:000005015"},{"id":"T12627","span":{"begin":44,"end":53},"obj":"GO_EXT:fatality_or_lethality"},{"id":"T12626","span":{"begin":31,"end":43},"obj":"GO:0007566"}],"text":"The underlying cause of the preimplantation lethality in Capn2-/- embryos has not yet been clarified. The two homozygous null embryos identified at the 8-cell stage did not present any obvious morphological defects. However, the fact that only two out of 90 successfully genotyped pre-implantation embryos proved to be Capn2-/- is in itself revealing. Preimplantation lethality resulting from gene knockouts can typically be attributed to two general causes. In some cases, defects are incurred in the embryonic differentiation program which can often be observed morphologically [38]. Null embryos of this type often survive beyond the morula stage, and a Mendelian distribution of embryonic genotypes is usually noted. In other cases, however, the gene disruption is thought to compromise fatally the viability of cells in the early embryo [3,39-43]. In these instances, only a few null embryos are ever observed and homozygous mutant ES cells could not be isolated. The Capn2 knockout fits into the latter category. If it is true that m-calpain is essential for some aspect of cell viability, the survival of a few Capn2-/- embryos to the 8-cell stage is most likely due to the persistence of some maternal m-calpain mRNA and/or protein through 2–3 cell divisions."}