Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region |
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Authors: | Junichiro Irie Yuehong Wu David A Sass William M Ridgway |
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Institution: | (1) Division of Rheumatology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA |
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Abstract: | Anti-Smith (anti-Sm) autoantibodies are directed to proteins in the small-nuclear ribonucleoprotein (snRNP) family and are
considered specific for systemic lupus erythematosus (SLE) in both humans and mice. We previously established that NOD.c3c4
mice, carrying B6 and B10 congenic segments from chromosomes 3 to 4 on an nonobese diabetic (NOD) background, and NOD.Idd9R28 mice, carrying a B10 segment on c4 alone, developed significant penetrance of anti-Sm antibody production. Here we determine
autoantibody incidence in additional NOD.Idd9 congenic strains and use a congenic mapping approach to narrow the interval necessary for enhanced autoantibody production
to a ∼5.6-Mb region containing insulin-dependent diabetes (Idd)9.3. The Idd9.3 interval contains the candidate molecule cluster of differentiation (CD)137, which is a member of the tumor necrosis factor
(TNF) receptor superfamily, functions as an inducible costimulator of T cells, and controls T–B interactions. The NOD and
B10 CD137 alleles have sequence polymorphisms and different functional effects on T cells; the NOD CD137 allele mediates weaker T cell proliferative responses and decreased interleukin (IL)-2 production after CD137-mediated costimulation.
Our work establishes CD137 as a candidate gene for control of autoantibody production in NOD.Idd9.3 congenic mice. |
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Keywords: | CD137 Autoantibodies Anti-Sm antibodies SLE Nonobese diabetic mouse Congenic mice |
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