This technology includes mouse models (heterozygous for the knock-in (KI) and homozygous for the knock-out (KO)) to be used as research reagents and to study molecular mechanisms and potential therapies for Familial Mediterranean fever (FMF). FMF is the prototype of a group of inherited disorders characterized by recurring, spontaneous episodes of fever and localized inflammation. The gene responsible for FMF is composed of 10 exons encoding a 781 amino acid protein known as pyrin. In addition to FMF, some recent findings show that an abnormal activation of the pyrin inflammasome is the inflammation inducing factor for seemingly distinct autoinflammatory disorder, hyperimmunoglobulinemia D syndrome, and a mutation in pyrin is also a genetic risk factor for pyrin-associated autoinflammation and neutrophilic dermatosis. Thus, these murine models may be used to evaluate other autoinflammatory disorders in addition to FMF.
Previous pyrin-deficient mice models develop normally and exhibit no overt phenotype; however, these models support a gain-of-function model with a gene-dosage effect, display varying disease severity, and can be used to investigate innate immune responses in autoinflammatory diseases other than FMF.