Inflammation in mice ectopically expressing human Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome-associated PSTPIP1 A230T mutant proteins
Authors
Wang, DonghaiHoing, Susanne
Patterson, Heide Christine
Ahmad, Umtul M.
Rathinam, Vijay A. K.
Rajewsky, Klaus
Fitzgerald, Katherine A.
Golenbock, Douglas T.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2013-02-15Keywords
Acne VulgarisAdaptor Proteins, Signal Transducing
Alleles
Animals
Arthritis, Infectious
Autoimmune Diseases
Caspase 1
Cytokines
Cytoskeletal Proteins
Gene Expression Regulation
Humans
Immunity, Innate
Inflammation
Interleukin-1beta
Mice
Mice, Inbred C57BL
Mice, Knockout
*Mutation
Phenotype
Pyoderma Gangrenosum
Signal Transduction
Syndrome
Turpentine
Biochemistry
Immunology and Infectious Disease
Metadata
Show full item recordAbstract
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. Results 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.Source
J Biol Chem. 2013 Feb 15;288(7):4594-601. doi: 10.1074/jbc.M112.443077. Link to article on publisher's siteDOI
10.1074/jbc.M112.443077Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29622PubMed ID
23293022Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M112.443077