Casp8 Conditional Knockout mouse models

As the apical death receptor caspase, mouse Casp8 is the ortholog of human CASP8 and carries tandem death effector domains that dock onto FADD within FAS, TRAIL receptor, or TNFR1 complex II, where dimerization and cleavage at Asp387 yield an active protease that processes BID and caspases 3 and 7. Equally important is its non-apoptotic role: caspase-8 cleaves RIPK1 and CYLD to restrain RIPK3 and MLKL dependent necroptosis, and it participates in FADD dependent inflammasome regulation. Germline deletion is embryonic lethal around E10.5 with yolk sac vascular failure, and that lethality is rescued by concurrent Ripk3 or Mlkl loss, the standard genetic proof that unrestrained necroptosis rather than lost apoptosis kills the embryo. Conditional flox alleles with epithelial or myeloid Cre are therefore mandatory for adult work, catalytically inactive C362A knockins isolate scaffolding, and human CASP8 knockins support study of patient variants causing lymphoproliferation and immunodeficiency.

A floxed Casp8 allele paired with Cre gives spatial control that whole body knockouts cannot offer. People use it to separate developmental roles from adult homeostasis, to model somatic mutations, and to match disease that begins in one organ.