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Inflammation in mice ectopically expressing human PAPA syndrome-associated PSTPIP1 A230T mutant proteins

Item Type:Article
Title:Inflammation in mice ectopically expressing human PAPA syndrome-associated PSTPIP1 A230T mutant proteins
Creators Name:Wang, D. and Höing, S. and Patterson, H.C. and Ahmad, U.M. and Rathinam, V.A.K. and Rajewsky, K. and Fitzgerald, K.A. and Golenbock, D.T.
Abstract:Pyogenic Arthritis, Pyoderma Gangrenosum and Acne Syndrome (PAPA syndrome) is an autoinflammatory disease caused by aberrant production of the proinflammatory cytokine interleukin-1. Mutations in the gene encoding proline serine threonine phosphatase interacting protein-1 (PSTPIP1) have been linked to PAPA syndrome. PSTPIP1 is an adaptor protein that interacts with PYRIN, the protein encoded by the Mediterranean Fever (MEFV) gene whose mutations cause Familial Mediterranean Fever (FMF). However, the pathophysiological function of PSTPIP1 remains to be elucidated. We have generated mouse strains that either are PSTPIP1 deficient or ectopically express mutant PSTPIP1. Rusults from analyzing these mice suggested that PSTPIP1 is not an essential regulator of the Nlrp3, Aim2 or Nlrc4 inflammasomes. Although common features of human PAPA syndrome such as pyogenic arthritis and skin inflammation were not recapitulated in the mouse model, ectopic expression of the mutant but not the wild type PSTPIP1 in mice lead to partial embryonic lethality, growth retardation and elevated level of circulating proinflammatory cytokines.
Keywords:Genetic Diseases, Immunology, Inflammation, Innate Immunity, Signal Transduction, Autoinflammatory Diseases, Inflammasome, Animals, Mice
Source:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Page Range:4594-4601
Date:15 February 2013
Official Publication:https://doi.org/10.1074/jbc.M112.443077
PubMed:View item in PubMed

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