RGD Reference Report - Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex. - Rat Genome Database

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Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.

Authors: Colle, E  Guttmann, RD  Seemayer, T 
Citation: Colle E, etal., J Exp Med 1981 Oct 1;154(4):1237-42
RGD ID: 61076
Pubmed: PMID:7026724   (View Abstract at PubMed)
PMCID: PMC2186484   (View Article at PubMed Central)

A syndrome of spontaneous diabetes mellitus has been previously described in a partially inbred rat strain called BB Wistar. We have determined whether there is major histocompatibility complex (MHC) linkage as well as other predisposing haplotype-associated factors of development. BB rats are RT1 (MHC) genotype u/u. Using BB x Lewis F1 hybrid matings, an F2 study analyzed 128 rats from 8 primary and 3 additional litters from a breeding pair producing a diabetic offspring. 4 of 128 F2 rats, all from the 48 progeny of same breeding pair, became clinically diabetic. The four diabetics were all genotype u/u (P = 0.03). In the primary F2 litters, haplotype distribution was not different from the 1:2:1 expected ratio. However, in the four litters from the from the F1 breeding pair producing diabetics, there was an increased number of u/u animals. Two-way analysis of variance revealed significant differences in pancreatic insulin content between litters (diabetics excluded), P less than 0.001, and between haplotypes P less than 0.007 with heterozygous u/u less than 1/1 progeny. The glucagon content showed no significant differences. These data demonstrate (a) MHC linkage with spontaneous diabetes in this rat model; (b) penetrance similar to the human disease; and (c) a possible association of MHC haplotype with pancreatic inflammation as well as insulin content in nondiabetic F2 siblings.

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
increased circulating glucose level  QTM 61076 RGD 
Objects Annotated

QTLs
Iddm1  (Insulin dependent diabetes mellitus QTL 1)

Objects referenced in this article
Strain BB/N BioBreeding rat Rattus norvegicus
Strain BBDP/Hri null Rattus norvegicus
Strain BBDP/Rhw null Rattus norvegicus
Strain BBDR/Rhw null Rattus norvegicus
Strain F344/NRrrc null Rattus norvegicus
Strain LEW Lewis Rattus norvegicus

Additional Information