Casp3 Conditional Knockout mouse models

Casp3 is the mouse ortholog of human CASP3 and encodes the principal executioner caspase, a short-prodomain zymogen activated by caspase-9 within the APAF1 apoptosome or by caspase-8 downstream of death receptors, then cleaving several hundred substrates including PARP1, the ICAD inhibitor of DFF40 whose removal unleashes internucleosomal DNA fragmentation, gelsolin, ROCK1 for membrane blebbing, and pannexin-1 for find-me signal release. Beyond death it mediates non-apoptotic events such as myoblast and osteoblast differentiation and dendritic spine pruning. Phenotype is strongly background dependent: on 129 the null shows exencephaly and perinatal lethality with excess neural progenitors, whereas on C57BL/6 mice are largely viable, so congenic state must be reported. Casp7 provides partial redundancy for a subset of substrates and compound Casp3 Casp7 alleles are needed for complete blockade. Use conditional flox designs with tissue Cre for lineage-restricted death questions, and catalytic mutant knockins when scaffold versus protease function is at issue.

Casp3 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.