Caspase 1 (also known as interleukin-1beta converting enzyme or ICE) knockout mice lack part of exons 6 and 7 of the Casp1 gene and do not process pro-IL-1beta (IL1B) or pro-IL-18 (IL18) into their mature forms. Therefore, stimulation of CASP1-deficient monocytes by activators of multiple pattern recognition receptors that form inflammasomes with CASP1 (including Nlrp3 and Nlrc4) fail to secrete mature IL1B or IL18. In addition, secretion of IL-1alpha (IL1A) is reduced. Caspase-1 is involved in particular cell death pathways including pyroptosis, and caspase-1 deficient cells demonstrate reduced lysis upon infection with certain pathogens.
It has recently been confirmed that these mice are de facto Casp1/Casp4(formerly called caspase 11) double knockout mice. This is resultant from the dysfunctional nature of the naturally occuring 129 Casp4 allele. These Casp1 knockout mice were produced in embryonic stem (ES) cells on a 129S2 background.
Homozygous Casp1 targeted mutant mice are viable, fertile, and show no gross abnormalities in appearance, body weight or organ size for at least the first 16 weeks of life. Homozygotes are born at predicted Mendelian frequencies and the absence of mRNA was confirmed by RT-PCR analysis.
