A non-MHC locus essential for autoimmune type I diabetes in the Komeda Diabetes-Prone rat

J Clin Invest. 1997 Oct 15;100(8):2015-21. doi: 10.1172/JCI119733.


The Long-Evans Tokushima Lean (LETL) rat, characterized by rapid onset of insulin-dependent (type I) diabetes mellitus (IDDM), no sex difference in the incidence of IDDM, autoimmune destruction of pancreatic beta cells, and no significant T cell lymphopenia, is a desirable animal model for human IDDM. We have established a diabetes-prone substrain of the LETL rat, named Komeda Diabetes-Prone (KDP) rat, showing a 100% development of moderate to severe insulitis within 220 d of age. The cumulative frequency of IDDM was 70% at 120 d of age, and reached 82% within 220 d of age. Here, we performed the first genome-wide scan for non-MHC IDDM susceptibility genes in this strain. The analysis of three crosses has led to the revelation of a major IDDM susceptibility gene, termed Iddm/kdp1, on rat chromosome (Chr) 11. Homozygosity for the KDP allele at this locus is shown to be essential for the development of moderate to severe insulitis and the onset of IDDM. Comparative mapping suggests that the homologues of Iddm/ kdp1 are located on human Chr 3 and mouse Chr 16 and would therefore be different from previously reported IDDM susceptibility genes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3
  • Crosses, Genetic
  • Diabetes Mellitus, Type 1 / etiology
  • Diabetes Mellitus, Type 1 / genetics*
  • Disease Susceptibility
  • Genetic Linkage
  • Genetic Markers
  • Genome
  • Genotype
  • Haplotypes
  • Homozygote
  • Humans
  • Islets of Langerhans / pathology*
  • Mice
  • Pancreatitis / genetics*
  • Rats
  • Rats, Inbred Strains
  • Severity of Illness Index
  • Species Specificity


  • Genetic Markers