FVB/N (H2(q)) mouse is resistant to arthritis induction and exhibits a genomic deletion of T-cell receptor V beta gene segments.
Animal models of autoimmune diseases have been instrumental in advancing our understanding of autoimmunity in humans. Collagen-induced arthritis (CIA) in mice is an autoimmune disease model of rheumatoid arthritis. Susceptibility to CIA in mice is linked to genes of the major histocompatibility complex (MHC). CD4(+) T cells that express the T-cell receptor (TCR) Tcra-V11.1 and/or Tcrb-V8.2 play a key role in the pathogenesis of arthritis in the DBA/1 mouse (H2(q)). We identified an inbred mouse strain, FVB/NJ (H2(q)), that is resistant to arthritis induction and exhibits a genomic deletion of certain Tcrb-V gene segments. We report a novel polymerase chain reaction-based method for the rapid identification of new mouse strains that exhibit germline Tcrb-V gene deletions. We mapped for the first time both the 5' and 3' breakpoints of the Tcrb-V deletion in the FVB/NJ, SWR, SJL, C57L, and C57BR strains to within 1.1 kilobases. Since there is an association between a particular Tcra-V allele (Tcra-V11.1(d)) and arthritis susceptibility in H2(q) mouse strains, we examined the allelic polymorphisms of the Tcra-V11 gene subfamily members between the arthritis-susceptible DBA/1 mouse and the arthritis-resistant FVB/NJ mouse strain. The amino acid sequences of the Tcra-V11.1 alleles differ at two positions (codons 18 and 68). Therefore, the resistance of FVB/NJ mouse to arthritis induction may be due in part to Tcra-V11.1 coding sequence polymorphism and Tcrb-V8.2 gene segment deletion, as we have recently demonstrated in the case of SWR mouse strain.
Osman
G E
GE
Department of Molecular Biotechnology, Box 357650, University of Washington School of Medicine, Seattle, WA 98195, USA. gamal@u.washington.edu
Hannibal
M C
MC
Anderson
J P
JP
Lasky
S R
SR
Ladiges
W C
WC
Hood
L
L
D000595:Amino Acid Sequence; D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D001483:Base Sequence; D003094:Collagen / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003094:Collagen