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 ou r understanding of autoimmunity in humans. Collagen-induced arthritis (CIA) in mice is an autoimmune disease model of rheumatoid arthritis. Susceptibi lity to CIA in mice is linked to genes of the major histocompatibility comp lex (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 D BA/1 mouse (H2(q)). We identified an inbred mouse strain, FVB/NJ (H2(q)), t hat is resistant to arthritis induction and exhibits a genomic deletion of certain Tcrb-V gene segments. We report a novel polymerase chain reaction-b ased 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' an d 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 betwee n a particular Tcra-V allele (Tcra-V11.1(d)) and arthritis susceptibility i n H2(q) mouse strains, we examined the allelic polymorphisms of the Tcra-V1 1 gene subfamily members between the arthritis-susceptible DBA/1 mouse and the arthritis-resistant FVB/NJ mouse strain. The amino acid sequences of th e 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 t o Tcra-V11.1 coding sequence polymorphism and Tcrb-V8.2 gene segment deleti on, as we have recently demonstrated in the case of SWR mouse strain.