Autoinflammatory diseases also known as cryopyrin-associated periodic syndromes (CAPS) like Muckle-Wells syndrome, familial cold autoinflammatory syndrome (FCAS) or neonatal-onset multisystem inflammatory disease (NOMID) are characterized by a pathological activation of the innate immune system, resulting in recurrent inflammation, fever, or serious accumulation of amyloid protein in organs.
Nlrp3A350VneoR mice (JAX# 017969) contain a floxed neomycin cassette (neoR) in opposite orientation to a point mutation in exon 3 of the cryopyrin (Nlrp3) gene. The mutation results in the A350V missense mutation, that corresponds to the human amino acid 352. When animals are bred to Cre recombinase expressing mice, neoR is deleted and the mutant Nlrp3A350V gene is expressed in all cre-containing tissues. Animals are widely used as model of CAPS.
Animals’ phenotype strongly depends on the promoter of the Cre recombinase mouse model utilized for crossbreeding. Using a tamoxifen-inducible promoter with Cre recombinase fused to the estrogen responsive protein allows variable Nlrp3A350V expression.
When Nlrp3A350V is expressed in adult animals, the following phenotype can be observed:
- Steady weight loss of 25% within 30 days
- Dermatitis with erythema and occasional ulceration
- Neutrophilic infiltrates in the spleen with increased levels of GR-1/CD11b double-positive cells
- Peripheral blood leukocytosis (neutrophilia)
- Mild anemia
- Increased serum IL-6 levels
- Variable IL-1β and TNF-α levels