Genetic complementation in female (BXSB x NZW)F2 mice.
F(1) hybrids among New Zealand Black (NZB), New Zealand White (NZW), and BXSB lupus-prone strains develop accelerated autoimmunity in both sexes regardless of the specific combination. To identify BXSB susceptibility loci in the absence of the Y chromosome accelerator of autoimmunity (Yaa) and to study the genetics of this complementation, genome-wide quantitative trait locus (QTL) mapping was performed on female (BXSB x NZW)F(2) mice. Six QTL were identified on chromosomes 1, 4, 5, 6, 7, and 17. Survival mapped to chromosomes 5 and 17, anti-chromatin Ab to chromosomes 4 and 17, glomerulonephritis to chromosomes 6 and 17, and splenomegaly to chromosomes 1, 7, and 17. QTL on chromosomes 4 and 6 were new and designated as Lxw1 and -2, respectively. Two non-MHC QTL (chromosomes 1 and 4) were inherited from the BXSB and the rest were NZW-derived, including two similar to previously defined loci. Only two of 11 previously defined non-MHC BXSB QTL using male (Yaa(+)) crosses were implicated, suggesting that some male-defined BXSB QTL may require coexpression of the Yaa. Findings from this and other studies indicate that BXSB and NZB backgrounds contribute completely different sets of genes to complement NZW mice. Identification of susceptibility genes and complementing genes in several lupus-prone strain combinations will be important for defining the epistatic effects and background influences on the heterogeneous genetic factors responsible for lupus induction.
Kono
Dwight H
DH
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA. dkono@scripps.edu
Park
Miyo S
MS
Theofilopoulos
Argyrios N
AN
D000818:Animals; D001167:Arteritis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D002843:Chromatin / Q000276:immunology; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005260:Female; D005816:Genetic Complementation Test / Q000379:methods; D008040:Genetic Linkage / Q000276:immunology; D020022:Genetic Predisposition to Disease; D016678:Genome; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology* / Q000401:mortality; D051379:Mice; D008814:Mice, Inbred NZB / Q000235:genetics* / Q000276:immunology*; D009203:Myocardial Infarction / Q000235:genetics / Q000276:immunology; D040641:Quantitative Trait Loci / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index; D013163:Splenomegaly / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis
D001323:Autoantibodies; D002843:Chromatin