title: Identification of chromosome intervals from 129 and C57BL/6 mouse strains linked to the development of systemic lupus erythematosus.
abstract: Systemic lupus erythematosus is an autoimmune disease in which complex interactions between genes and environmental factors determine the disease phenotype. We have shown that genes from the non-autoimmune strains 129 and C57BL/6 (B6), commonly used for generating gene-targeted animals, can induce a lupus-like disease. Here, we conducted a genome-wide scan analysis of a cohort of (129 x B6)F2 C1q-deficient mice to identify loci outside the C1qa locus contributing to the autoimmune phenotype described in these mice. The results were then confirmed in a larger dataset obtained by combining the data from the C1q-deficient mice with data from previously reported wild-type mice. Both analyses showed that a 129-derived interval on distal chromosome 1 is strongly linked to autoantibody production. The B6 genome contributed to anti-nuclear autoantibody production with an interval on chromosome 3. Two regions were linked to glomerulonephritis: a 129 interval on proximal chromosome 7 and a B6 interval on chromosome 13. These findings demonstrate that interacting loci between 129 and B6 mice can cause the expression of an autoimmune phenotype in gene-targeted animals in the absence of any disrupted gene. They also indicate that some susceptibility genes can be inherited from the genome of non-autoimmune parental strains.
authors.affiliation: Molecular Genetics and Rheumatology Section, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Heidari
authors.forename: A E
authors.initials: AE
authors.lastname: Bygrave
authors.forename: R J
authors.initials: RJ
authors.lastname: Rigby
authors.forename: K L
authors.initials: KL
authors.lastname: Rose
authors.forename: M J
authors.initials: MJ
authors.lastname: Walport
authors.forename: H T
authors.initials: HT
authors.lastname: Cook
authors.forename: T J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: M
authors.initials: M
authors.lastname: Botto
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D002874:Chromosome Mapping; D015922:Complement C1q / Q000172:deficiency / Q000235:genetics; D005260:Female; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D040641:Quantitative Trait Loci; D013045:Species Specificity
chemical_list: D000974:Antibodies, Antinuclear; D015922:Complement C1q