title: Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in the BXD2 recombinant inbred strain of mice.
abstract: The BXD2 strain of mice is one of approximately 80 BXD recombinant inbred (RI) mouse strains derived from an intercross between C57BL/6J (B6) and DBA/2J (D2) strains. We have discovered that adult BXD2 mice spontaneously develop generalized autoimmune disease, including glomerulonephritis (GN), increased serum titres of rheumatoid factor (RF) and anti-DNA antibody, and a spontaneous erosive arthritis characterized by mononuclear cell infiltration, synovial hyperplasia, and bone and cartilage erosion. The features of lupus and arthritis developed by the BXD2 mice segregate in F2 mice generated by crossing BXD2 mice with the parental B6 and D2 strains. Genetic linkage analysis of the serum levels of anti-DNA and RF by using the BXD RI strains shows that the serum titers of anti-DNA and RF were influenced by a genetic locus on mouse chromosome (Chr) 2 near the marker D2Mit412 (78 cm, 163 Mb) and on Chr 4 near D4Mit146 (53.6 cm, 109 Mb), respectively. Both loci are close to the B-cell hyperactivity, lupus or GN susceptibility loci that have been identified previously. The results of our study suggest that the BXD2 strain of mice is a novel model for complex autoimmune disease that will be useful in identifying the mechanisms critical for the immunopathogenesis and genetic segregation of lupus and erosive arthritis.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, AL 35294, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Mountz
authors.forename: P
authors.initials: P
authors.lastname: Yang
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Tousson
authors.forename: A
authors.initials: A
authors.lastname: Fitzgerald
authors.forename: J
authors.initials: J
authors.lastname: Allen
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Cartner
authors.forename: W E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: N
authors.initials: N
authors.lastname: Yi
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: R W
authors.initials: RW
authors.lastname: Williams
authors.forename: H-C
authors.initials: HC
authors.lastname: Hsu
mesh_terms: D000419:Albuminuria; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001168:Arthritis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008040:Genetic Linkage / Q000276:immunology; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D008177:Lupus Vulgaris / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D040641:Quantitative Trait Loci / Q000235:genetics / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D012217:Rheumatoid Factor