RGD Reference Report - VIRUS-INDUCED AUTOIMMUNE DIABETES IN THE LEW.1WR1 RAT REQUIRES Iddm14 AND A GENETIC LOCUS PROXIMAL TO THE MAJOR HISTOCOMPATIBILITY COMPLEX. - Rat Genome Database

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VIRUS-INDUCED AUTOIMMUNE DIABETES IN THE LEW.1WR1 RAT REQUIRES Iddm14 AND A GENETIC LOCUS PROXIMAL TO THE MAJOR HISTOCOMPATIBILITY COMPLEX.

Authors: Blankenhorn, EP  Cort, L  Greiner, DL  Guberski, DL  Mordes, JP 
Citation: Blankenhorn EP, etal., Diabetes. 2009 Aug 31.
RGD ID: 2313174
Pubmed: (View Article at PubMed) PMID:19720792
DOI: Full-text: DOI:10.2337/db09-0387

Objective: To identify genes that confer susceptibility to autoimmune diabetes following viral infection in the LEW.1WR1 rat. Research Design and Methods: About 2% of LEW.1WR1 rats develop spontaneous autoimmune diabetes. Immunological perturbants including viral infection increase both the frequency and tempo of diabetes onset. To identify diabetes susceptibility genes, (LEW.1WR1 x WF) F2 rats were infected with Kilham rat virus following brief pre-treatment with polyinosinic:polycytidylic acid. This treatment induces diabetes in 100% of parental LEW.1WR1 rats and 0% of parental WF rats. Linkage to diabetes was analyzed by genome-wide scanning. Results: Among 182 F2 rats, 57 (31%) developed autoimmune diabetes after a mean latency of 16 days. All diabetic animals and approximately 20% of non-diabetic animals exhibited pancreatic insulitis. Genome-wide scanning revealed a requirement for the Iddm14 locus, long known to be required for diabetes in the BB rat. In addition, a new locus near the RT1 major histocompatibility complex was found to be a major determinant of disease susceptibility. Interestingly, one gene linked to autoimmune diabetes in mouse and human, UBD, lies within this region. Conclusions: The Iddm14 diabetes locus in the rat is a powerful determinant of disease penetrance in the LEW.1WR1 rat following viral infection. In addition, a locus near the MHC (Iddm37) conditions diabetes susceptibility in these animals. Other, as yet unidentified, genes are required to convert latent susceptibility to overt diabetes. These data provide insight into the polygenic nature of autoimmune diabetes in the rat and the interplay of genetic and environmental factors underlying disease expression.

Annotation

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
insulitis  (IDA)
Objects Annotated

QTLs
Iddm37  (Insulin dependent diabetes mellitus QTL 37)

Objects referenced in this article
0 Iddm14 Insulin dependent diabetes mellitus QTL 14 All species
0 Iddm20 Insulin dependent diabetes mellitus QTL 20 All species
0 LEW.1WR1/WorBrm null All species
0 WF.ART2/Wor null All species

Additional Information