title: Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats.
abstract: Although the MHC class II 'u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II 'a' and 'u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II 'a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis.
authors.affiliation: Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan. yokoi@med.kobe-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Yokoi
authors.forename: S
authors.initials: S
authors.lastname: Hidaka
authors.forename: S
authors.initials: S
authors.lastname: Tanabe
authors.forename: M
authors.initials: M
authors.lastname: Ohya
authors.forename: M
authors.initials: M
authors.lastname: Ishima
authors.forename: Y
authors.initials: Y
authors.lastname: Takagi
authors.forename: N
authors.initials: N
authors.lastname: Masui
authors.forename: S
authors.initials: S
authors.lastname: Seino
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D009154:Mutation; D051381:Rats; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D000949:Histocompatibility Antigens Class II