Epistatic suppression of systemic lupus erythematosus: fine mapping of Sles1 to less than 1 mb.
Sle is a susceptibility locus for systemic autoimmunity derived from the lupus-prone NZM2410 mouse. The New Zealand White-derived suppressive modifier Sles1 was identified as a specific modifier of Sle1 and prevents the development of IgG anti-chromatin autoantibodies mediated by Sle1 on the C57BL/6 (B6) background. Fine mapping of Sles1 with truncated congenic intervals localizes it to a approximately 956-kb segment of mouse chromosome 17. Sles1 completely abrogates the development of activated T and B cell populations in B6.Sle1. Despite this suppression of the Sle1-mediated cell surface activation phenotypes, B6.Sle1 Sles1 splenic B cells still exhibit intrinsic ERK phosphorylation. Classic genetic complementation tests using the nonautoimmmune 129/SvJ mouse suggests that this strain possesses a Sles1 allele complementary to that of New Zealand White, as evidenced by the lack of glomerulonephritis, splenomegaly, and antinuclear autoantibody production seen in (129 x B6.Sle1 Sles1)F(1)s. These findings localize and characterize the suppressive properties of Sles1 and implicate 129 as a useful strain for aiding in the identification of this elusive epistatic modifier gene.
Subramanian
Srividya
S
Center for Immunology and Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Yim
Young-Sun
YS
Liu
Kui
K
Tus
Katalin
K
Zhou
Xin J
XJ
Wakeland
Edward K
EK
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004843:Epistasis, Genetic; D005260:Female; D005816:Genetic Complementation Test; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008815:Mice, Inbred Strains; D020161:Physical Chromosome Mapping / Q000379:methods*; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013489:Suppression, Genetic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000954:Antigens, Surface; D014409:Tumor Necrosis Factor-alpha