| Autor: |
Bill, Giannakopoulos, Peyman, Mirarabshahi, Miao, Qi, Chris, Weatherall, Jian Cheng, Qi, Kumiko, Tanaka, Ewan, Millar, Leon, Vonthethoff, Dominique, Gatto, Derek, Spielman, Steven A, Krilis |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
Arthritisrheumatology (Hoboken, N.J.). 66(8) |
| ISSN: |
2326-5205 |
| Popis: |
The BXSB.Yaa mouse strain is a model of systemic lupus erythematosus that is dependent on duplication of the Toll-like receptor 7 gene. The objective of this study was to systematically describe the amplified autoimmune phenotype observed when the soluble plasma protein β2 -glycoprotein I (β2 GPI) gene was deleted in male BXSB.Yaa mice.We generated BXSB.Yaa and NZW mouse strains in which the β2 GPI gene had been knocked out by backcrossing the wild-type strains with C57BL/6 β2 GPI(-/-) mice for 10 generations. Sex- and age-matched mice of the various strains were housed under identical conditions and were killed at fixed time intervals. Serum and tissue specimens were collected at various time points. Lupus-associated autoantibodies, inflammatory cytokines, and the type I interferon (IFN) gene signature were measured. Flow cytometric analyses of lymphocyte populations were performed. The severity of glomerulonephritis was graded by 2 independent renal histopathologists.Male BXSB.Yaa β2 GPI(-/-) mice developed significant lymphadenopathy and splenomegaly compared with age-matched controls. Male BXSB.Yaa β2 GPI(-/-) mice also had significantly higher levels of autoantibodies, increased levels of inflammatory cytokines including tumor necrosis factor α, interleukin-6, and BAFF, and more severe glomerulonephritis. The type I IFN gene signature in male BXSB.Yaa β2 GPI(-/-) mice was significantly higher than that in control mice. Male BXSB.Yaa β2 GPI(-/-) mice also had marked dysregulation of various B cell and T cell populations in the spleens and lymph nodes and a disturbance in apoptotic cell clearance.Deletion of β2 GPI accelerates and potentiates the autoimmune phenotype in male BXSB.Yaa mice. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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