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 H2g7 Complex

  1. Darcy P. Pomerleau1,
  2. Rebecca J. Bagley1,
  3. David V. Serreze1,
  4. Clayton E. Mathews2 and
  5. Edward H. Leiter1
  1. 1The Jackson Laboratory, Bar Harbor, Maine
  2. 2University of Pittsburgh, Department of Pediatrics, Pittsburgh, Pennsylvania
  1. Address correspondence and reprint requests to Dr. Edward H. Leiter, The Jackson Laboratory, 600 Main St, Bar Harbor, ME 04609. E-mail: ehl{at}


The diabetogenic major histocompatibility complex (MHC) (H2g7) of NOD mice comprises contributions from several class II loci collectively designated as Idd1. Introduction of the H2gx 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 H2gx haplotype, which does not differ from H2g7 from the class I H2-Kd 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-Ddx rather than the H2g7 encoded Db allele. Two differential-length NOD.ALR-H2gx congenic stocks (D.R1 and D.R2), both containing H2-Ddx, 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-Ddx MHC class I variant present in both diabetes-resistant stocks, but not the susceptible stock, is discussed.


    • Accepted February 16, 2005.
    • Received November 12, 2004.
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