RGD Reference Report - The rat diabetes susceptibility locus Iddm4 and at least one additional gene are required for autoimmune diabetes induced by viral infection. - Rat Genome Database

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The rat diabetes susceptibility locus Iddm4 and at least one additional gene are required for autoimmune diabetes induced by viral infection.

Authors: Blankenhorn, EP  Rodemich, L  Martin-Fernandez, C  Leif, J  Greiner, DL  Mordes, JP 
Citation: Blankenhorn EP, etal., Diabetes 2005 Apr;54(4):1233-7.
RGD ID: 1358924
Pubmed: PMID:15793267   (View Abstract at PubMed)
PMCID: PMC2518668   (View Article at PubMed Central)

BBDR rats develop autoimmune diabetes only after challenge with environmental perturbants. These perturbants include polyinosinic:polycytidylic acid (poly I:C, a ligand of toll-like receptor 3), agents that deplete regulatory T-cell (Treg) populations, and a non-beta-cell cytopathic parvovirus (Kilham rat virus [KRV]). The dominant diabetes susceptibility locus Iddm4 is required for diabetes induced by treatment with poly I:C plus Treg depletion. Iddm4 is penetrant in congenic heterozygous rats on the resistant WF background and is 79% sensitive and 80% specific as a predictor of induced diabetes. Surprisingly, an analysis of 190 (BBDR x WF)F2 rats treated with KRV after brief exposure to poly I:C revealed that the BBDR-origin allele of Iddm4 is necessary but not entirely sufficient for diabetes expression. A genome scan identified a locus on chromosome 17, designated Iddm20, that is also required for susceptibility to diabetes after exposure to KRV and poly I:C (logarithm of odds score 3.7). These data suggest that the expression of autoimmune diabetes is a complex process that requires both major histocompatibility complex genes that confer susceptibility and additional genes such as Iddm4 and Iddm20 that operate only in the context of specific environmental perturbants, amplifying the immune response and the rate of disease progression.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Iddm20RatExperimental Diabetes Mellitus  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Iddm20Ratautoimmune response  IAGP  RGD 
Iddm20Rathyperglycemia  IAGP  RGD 

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Objects Annotated

QTLs
Iddm20  (Insulin dependent diabetes mellitus QTL 20)

Strains
BBDR/Wor  (NA)
WF.BBDR-ART2a/Wor  (Wistar Furth)

Objects referenced in this article
QTL Iddm14 Insulin dependent diabetes mellitus QTL 14 Rattus norvegicus

Additional Information