• NLRP3 (NLR family pyrin domain containing 3), is a member of nucleotide-binding domain-(NOD) like receptor family. Upon activation, the encoded protein interacts with the apoptosis-associated speck-like protein PYCARD/ASC, which contains a caspase recruitment domain, and assemble into a multimeric protein, called the NLRP3 inflammasome. The inflammasome then promotes inflammation and pyroptotic cell death.
• The exons 1-10 of mouse Nlrp3 gene that encode whole protein is replaced by human counterparts in B-hNLRP3 mice. The promoter, 5’UTR and 3’UTR region of the mouse Nlrp3 are also replaced by human counterparts. The NLRP3 expression is driven by endogenous human NLRP3 promoter, while mouse Nlrp3 gene transcription and translation will be disrupted.
• Mouse Nlrp3 mRNA was detectable in wild-type C57BL/6JNifdc mice. Human NLRP3 mRNA was detectable in homozygous B-hNLRP3 mice.
• Application: This product is used for preclinical safety evaluation of antibody drugs.

Gene targeting strategy for B-hNLRP3 mice. The exons 1-10 of mouse Nlrp3 gene that encode whole protein is replaced by human counterparts in B-hNLRP3 mice. The promoter, 5’UTR and 3’UTR region of the mouse Nlrp3 are also replaced by human counterparts. The NLRP3 expression is driven by endogenous human NLRP3 promoter, while mouse Nlrp3 gene transcription and translation will be disrupted.

Strain specific analysis of NLRP3 mRNA expression in wild-type C57BL/6JNifdc mice and B-hNLRP3 mice by RT-PCR. Spleen RNA was isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hNLRP3 mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human NLRP3 primers. Mouse Nlrp3 mRNA was only detectable in wild-type mice. Human NLRP3 mRNA was exclusively detectable in homozygous B-hNLRP3 mice but not in wild-type mice.

Function analysis of NLRP3 in homozygous B-hNLRP3 mice by ELISA. Plasma was collected from homozygous B-hNLRP3 mice (H/H)  (male, n=1, 10-week-old). B-hNLRP3 mice was stimulated by 10 mg/kg LPS for 4 h. MCC950 (Selleck MCC950 Sodium, S7809)  was injected 1h before LPS injection (both i.p.). Expression level of mouse IL1β were analyzed by ELISA (BioLegend ELISA MAX™ Deluxe Set Mouse IL-1β, 432604). The result showed that mouse IL1β in the downstream pathway was largely reduced by NLRP3 inhibitor MCC950, indicating a successful inhibition of the downstream activation caused by hNLRP3.