1. Главная
  2. Ресурсы
  3. Библиотечный поиск
HLA-DQ8 transgenicmice are highlysusceptible tocollagen-inducedarthritis: a novelmodel for humanpolyarthritis. Gerald NaboznyJeanine BaischCheng Shen1996 год

HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel model for human polyarthritis.
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: Genetic studies have indicated that susceptibility to rheumatoid arthritis (RA) maps to the HLA-DR locus of the major histocompatibility complex. Strong linkage disequilibrium between certain HLA-DQ genes and HLA-DR genes associated with RA, however, suggests that HLA-DQ molecules may also play a role in RA susceptibility. To examine the role of HLA-DQ molecules in arthritis, we generated transgenic mice expressing the DQA1*0301 and DQB1*0302 genes from an RA predisposing haplotype (DQ8/DR4Dw4). The transgenes were introduced into mouse class II-deficient H-2Ab0 mice, and their susceptibility to experimental collagen-induced arthritis was evaluated. The HLA-DQ8+,H-2Ab0 mice displayed good expression of the DQ8 molecule, while no surface expression of endogenous murine class II molecules could be detected. The DQ8 molecule also induced the selection of CD4+ T cells expressing a normal repertoire of V beta T cell receptors. Immunization of HLA-DQ8+,H-2Ab0 mice with bovine type II collagen (CII) induced a strong antibody response that was cross-reactive to homologous mouse CII. Also, in vitro proliferative responses against bovine CII, which were blocked in the presence of an antibody specific for HLA-DQ and mouse CD4, were detected. Finally, a severe polyarthritis developed in a majority of HLA-DQ8+,H-2Ab0 mice, which was indistinguishable from the disease observed in arthritis susceptible B10.T(6R) (H-2Aq) controls. In contrast, HLA-DQ8-,H-2Ab0 fullsibs did not generate CII antibody and were completely resistant to arthritis. Therefore, these results strongly suggest that HLA-DQ8 molecules contribute to genetic susceptibility to arthritis and also establish a novel animal model for the study of human arthritis.
Год издания: 1996
Авторы: Gerald Nabozny, Jeanine Baisch, Cheng Shen, Dominic Cosgrove, Marie Griffiths, Harvinder S. Luthra, Chella S. David
Издательство: Rockefeller University Press
Источник: The Journal of Experimental Medicine
Ключевые слова: Monoclonal and Polyclonal Antibodies Research, HER2/EGFR in Cancer Research
Другие ссылки: The Journal of Experimental Medicine (PDF)
The Journal of Experimental Medicine (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)