FVB/N (H2(q)) mouse is resistant to arthritis induction and exhibits a genomic deletion of T-cell receptor V beta gene segments

• Published in: Immunogenetics (New York) 1999-09, Vol.49 (10), p.851-859
• Main Authors: Osman, G E, Hannibal, M C, Anderson, J P, Lasky, S R, Ladiges, W C, Hood, L
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Arthritis - etiology; Arthritis - genetics; Arthritis - immunology; Base Sequence; Collagen - immunology; Disease Models, Animal; DNA Primers - genetics; Humans; Mice; Mice, Inbred Strains; Molecular Sequence Data; Polymorphism, Genetic; Receptors, Antigen, T-Cell, alpha-beta - genetics; Sequence Deletion; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Species Specificity; T-Lymphocytes - immunology
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s002510050564

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.