Casp1 Conditional Knockout mouse models

Casp1, ortholog of human CASP1, encodes the prototypic inflammatory caspase, a CARD-containing zymogen recruited to ASC filaments within NLRP3, NLRC4, AIM2, or pyrin inflammasomes, where proximity-induced dimerization and autoprocessing generate p20 and p10 catalytic species that cleave pro-IL-1beta and pro-IL-18 to mature cytokines and cut gasdermin D to liberate its pore-forming N-terminal fragment, causing pyroptosis and cytokine release. A crucial technical caveat is that most legacy Casp1 null lines derive from 129 embryonic stem cells and carry a passenger loss-of-function Casp11 (human CASP4) allele, so apparent Casp1 phenotypes may reflect combined canonical and noncanonical inflammasome deficiency unless a Casp11-intact or independently generated conditional allele is used. Catalytically dead C284A knockins separate scaffolding from proteolysis, conditional flox alleles with LysM or Cx3cr1 Cre assign the responsible myeloid compartment, and humanization serves inhibitor programs where active site chemistry differs between species.

Conditional deletion of Casp1 limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Casp1 floxed stock yields usable cohorts.