title: Genetic dissection of vasculitis, myeloperoxidase-specific antineutrophil cytoplasmic autoantibody production, and related traits in spontaneous crescentic glomerulonephritis-forming/Kinjoh mice.
abstract: The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse is a model of human crescentic glomerulonephritis and vasculitis associated with the production of the myeloperoxidase (MPO)-specific antineutrophil cytoplasmic autoantibody (MPO-ANCA). Although the disease is mediated initially by mutation of the Fas gene (lpr), SCG/Kj mice also have non-Fas predisposing genetic factors. To define these factors, genome-wide quantitative trait locus (QTL) mapping was performed on female (B(6)x SCG/Kj) F(2) intercross mice. Fourteen non-Fas QTLs were identified. QTLs of glomerulonephritis were located on chromosomes 1, 10, 13, 16, and 17, vasculitis on chromosomes 1 and 17, splenomegaly on chromosome 1, hypergammaglobulinemia on chromosomes 1, 2, 4, 6, 7, 11, 13, and 17, antinuclear Ab on chromosomes 1, 8, 10, and 12, and MPO-ANCA production on chromosomes 1 and 10. Significant QTLs derived from SCG/Kj on chromosomes 1, 2, 7, and 13 were designated Scg-1 to Scg-5, respectively, and those derived from B(6) on chromosomes 4, 6, 17, and 10 were designated Sxb-1 to Sxb-4, respectively. Two loci linked to MPO-ANCA production on chromosomes 1 and 10 were designated Man-1 and Man-2 (for MPO-ANCA), respectively. Although both Scg-1 and Scg-2 were on chromosome 1 and shared several functions, it was of interest that aberrant MPO-ANCA production was exclusively controlled by Man-1, the centromeric half region of the Scg-2 chromosomal segment. We also examined the epistatic effects between the lpr mutation and non-Fas susceptibility genes. QTLs are discussed in relation to previously described loci, with emphasis on their candidate genes.
authors.affiliation: Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. hamanoyoshitomo@jcom.home.ne.jp
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Hamano
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Abe
authors.forename: Guo Dong
authors.initials: GD
authors.lastname: Sun
authors.forename: Danqing
authors.initials: D
authors.lastname: Zhang
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Shuji
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Masumi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishida-Okawara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishimura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tokunaka
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirose
authors.forename: Kazuo
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000096:biosynthesis* / Q000276:immunology; D002875:Chromosomes / Q000235:genetics; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D005260:Female; D005838:Genotype; D005921:Glomerulonephritis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D009195:Peroxidase / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000235:genetics; D014657:Vasculitis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors; D009195:Peroxidase