Fas Conditional Knockout mouse models

Fas encodes CD95 (APO-1, TNFRSF6), the mouse ortholog of human FAS, a type I membrane death receptor whose three cysteine-rich extracellular domains bind trimeric FAS ligand and whose cytoplasmic death domain, after ligand-driven higher-order clustering, recruits FADD and procaspase-8 into the death-inducing signaling complex to initiate apoptosis directly and through BID cleavage. Outcome depends on receptor palmitoylation, lipid raft clustering, and CFLAR abundance, while non-apoptotic FAS signaling through NF-kappaB and ERK contributes to inflammation and proliferation. Mouse genetics here is historically rich: the lpr allele is a retrotransposon insertion causing aberrant splicing and near-complete loss, lprcg is a death domain point mutation, and both drive lymphadenopathy, autoantibodies, and background-dependent nephritis modeling human autoimmune lymphoproliferative syndrome. Faslg (gld) mutation phenocopies from the ligand side, so the axis is nonredundant. Use conditional flox alleles with T cell, B cell, or hepatocyte Cre for compartment questions and humanization for agonist or antagonist antibody programs.

Fas 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.