| First Author | Snouwaert JN | Year | 2016 |
| Journal | Cell Rep | Volume | 17 |
| Issue | 11 | Pages | 3077-3088 |
| PubMed ID | 27974218 | Mgi Jnum | J:241705 |
| Mgi Id | MGI:5903532 | Doi | 10.1016/j.celrep.2016.11.052 |
| Citation | Snouwaert JN, et al. (2016) An NLRP3 Mutation Causes Arthropathy and Osteoporosis in Humanized Mice. Cell Rep 17(11):3077-3088 |
| abstractText | The NLRP3 inflammasome plays a critical role in host defense by facilitating caspase I activation and maturation of IL-1beta and IL-18, whereas dysregulation of inflammasome activity results in autoinflammatory disease. Factors regulating human NLRP3 activity that contribute to the phenotypic heterogeneity of NLRP3-related diseases have largely been inferred from the study of Nlrp3 mutant mice. By generating a mouse line in which the NLRP3 locus is humanized by syntenic replacement, we show the functioning of the human NLRP3 proteins in vivo, demonstrating the ability of the human inflammasome to orchestrate immune reactions in response to innate stimuli. Humanized mice expressing disease-associated mutations develop normally but display acute sensitivity to endotoxin and develop progressive and debilitating arthritis characterized by granulocytic infiltrates, elevated cytokines, erosion of bones, and osteoporosis. This NLRP3-dependent arthritis model provides a platform for testing therapeutic reagents targeting the human inflammasome. |
