Nlrp3L351PneoR mice contain a floxed neomycin cassette in intron 2 of the NLR family, pyrin domain containing 3 gene, Nlrp3, in opposite orientation to gene (neoR), abolishing gene expression. These mice also contain a point mutation in exon 3, which results in a missense mutation, L351P, corresponding to human amino acid 353. This mutation is commonly found in humans with familial cold autoinflammatory syndrome (FCAS). NLRP3 encodes the protein cryopyrin, which is a cytosolic nucleotide-binding domain and leucine-rich repeat containing (NLR) protein expressed in white blood cells and chondrocytes. Cryopyrin controls the formation of the inflammasome which regulates the immune system's response to injury, toxins, and infection by cleaving interleukin (IL)-1β. NLRP3 mutations are known to cause autoinflammatory diseases known as cryopyrin-associated periodic syndromes (CAPS) such as FCAS, Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disease (NOMID). Homozygotes are viable and fertile and lack expression of Nlrp3 due to the presence of the neoR cassette. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have the floxed-neoR deleted in the cre-expressing tissues, allowing expression of the mutated gene.
For example, when bred to B6.129P2-Lyz2tm1(cre)Ifo/J mice (Stock No. 004781), Nlrp3L351PneoR expression in myeloid lineage cells results in 100% lethality by one day after birth.
When bred to B6.Cg-Tg(CAG-cre/Esr1*)5Amc/J mice (Stock No. 004682), bone marrow derived dendritic cells (DCs) spontaneously secrete high levels of IL-1β in response to cold (32 degrees) incubation.
