Pycard Conditional Knockout mouse models

Pycard, the mouse ortholog of human PYCARD, encodes ASC, a bipartite adaptor whose pyrin domain nucleates prion-like filaments with activated sensors including NLRP3, NLRC4, AIM2, and pyrin, while its CARD recruits and clusters pro-caspase-1 into the dense speck where proximity-induced autoproteolysis occurs. Mature caspase-1 then processes IL-1 beta and IL-18 and cleaves gasdermin D to open plasma membrane pores, and ASC specks released from dying cells continue to mature cytokines extracellularly, making ASC a signaling node rather than a passive linker. Nulls are viable and fertile, so straight deletion cleanly reports inflammasome dependence, conditional alleles assign requirement to macrophages, neutrophils, or epithelium, and phosphosite or filament-disrupting knockins separate speck assembly from caspase recruitment. Certain NLRC4 and NLRP1 responses proceed with reduced ASC dependence, so match the allele to endpoints such as IL-1 beta release, pyroptosis kinetics, or gout and peritonitis models.

A floxed Pycard 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.