Major histocompatibility complex-linked diabetes susceptibility in NOD/Lt mice: subcongenic analysis localizes a component of Idd16 at the H2-D end of the diabetogenic H2(g7) complex.
The diabetogenic major histocompatibility complex (MHC) (H2(g7)) of NOD mice comprises contributions from several class II loci collectively designated as Idd1. Introduction of the H2(gx) haplotype from the related but diabetes-resistant cataract Shionogi (CTS) strain demonstrated an additional MHC-linked locus designated Idd16. The NOD-related alloxan resistant (ALR)/Lt strain is also characterized by the H2(gx) haplotype, which does not differ from H2(g7) from the class I H2-K(d) gene distally through the class II and into the class III region. Polymorphisms distal to the heat shock protein 70 locus (Hspa1b) include a rare H2-D(dx) rather than the H2(g7) encoded D(b) allele. Two differential-length NOD.ALR-H2(gx) congenic stocks (D.R1 and D.R2), both containing H2-D(dx), significantly suppressed diabetogenesis. This protection was lost when ALR alleles between the class III region and H2-D were removed in a shorter interval congenic (D.R3). Because no differences were observed in the ALR-derived interval extending 0.41 mB proximal to H2-K in any of these congenic stocks, a component of what was originally designated "Idd16" was sited to an interval shorter than 7.33 mB, distinguishing D.R2 from D.R3. Evidence supporting the candidacy of the ALR/CTS-shared H2-D(dx) MHC class I variant present in both diabetes-resistant stocks, but not the susceptible stock, is discussed.
Pomerleau
Darcy P
DP
The Jackson Laboratory, 600 Main St, Bar Harbor, ME 04609, USA.
Bagley
Rebecca J
RJ
Serreze
David V
DV
Mathews
Clayton E
CE
Leiter
Edward H
EH
D000375:Aging; D000818:Animals; D015415:Biomarkers; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D015994:Incidence; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D012727:Sex Characteristics
D015415:Biomarkers