Genetic control by I-A subregion in H-2 complex of incidence of streptozocin-induced autoimmune diabetes in mice.
An experimental autoimmune diabetes in mice characterized by delayed-onset hyperglycemia with lymphocytic infiltrations of the pancreatic islets can be induced by multiple administrations of low doses of streptozocin (STZ). We report on the influence of the MHC (H-2 complex) on this autoimmune diabetes by comparing the susceptibilities of various congenic and recombinant strains with a B10 background. In congenic strains, C57BL/10 (H-2b) and B10.BR (H-2k) mice showed a high incidence of diabetes, whereas B10.D2 (H-2d) and B10.S (H-2s) mice showed a low incidence. Therefore, we suggest that the H-2 complex influences diabetes susceptibility and that both b and k are high-susceptibility alleles, whereas d and s are low-susceptibility alleles. In recombinant strains, those with the same haplotypes on the K, E, S, and D subregions of the H-2 complex showed undefined (high and low) susceptibilities, indicating that the diabetes-susceptibility genes are located outside these loci. Strains possessing I-Ab or I-Ak gene products (C57BL/10, B10.BR, B10.TL, B10.A, and B10.A(2R] showed high incidences, whereas strains possessing I-Ad or I-As (B10.D2, B10.S, B10.S(7R), B10.S(9R), and B10.GD) showed low incidences. In addition, administration of anti-I-A monoclonal antibody prevented the manifestation of diabetes in STZ-administered mice. Passive transfer of STZ-administered T lymphocytes to mice given minute doses of STZ induced significant hyperglycemia. This successful transfer was only observed in H-2-compatible mice. Thus, we conclude that one gene coding for susceptibility to this experimental diabetes was located in the I-A subregion within the H-2 complex.
Tanaka
S
S
Third Department of Internal Medicine, Yokohama City University School of Medicine, Japan.
Nakajima
S
S
Inoue
S
S
Takamura
Y
Y
Aoki
I
I
Okuda
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000235:genetics*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011995:Recombination, Genetic; D012016:Reference Values; D013311:Streptozocin / Q000633:toxicity
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D013311:Streptozocin