DESCRIPTION:

QTL Associated with Glucose level. On Chromosome 20 with a LOD score= 6, p-value =. From a(n) of

LABEL:

QTL-Iddm37-Rat-Chr 20

SCORE TYPE:

Binary

DATE ADDED:

2015-06-10

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Blankenhorn EP, Cort L, Greiner DL, Guberski DL, Mordes JP

TITLE:

Virus-induced autoimmune diabetes in the LEW.1WR1 rat requires Iddm14 and a genetic locus proximal to the major histocompatibility complex.

JOURNAL:

Diabetes None None, Vol 58, pp. 2930-8

ABSTRACT:

1. Diabetes. 2009 Dec;58(12):2930-8. doi: 10.2337/db09-0387. Epub 2009 Aug 31. Virus-induced autoimmune diabetes in the LEW.1WR1 rat requires Iddm14 and a genetic locus proximal to the major histocompatibility complex. Blankenhorn EP(1), Cort L, Greiner DL, Guberski DL, Mordes JP. Author information: (1)Department of Microbiology and Immunology, Center for Immunogenetics and Inflammatory Diseases, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA. eblanken@drexelmed.edu 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 pretreatment 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 nondiabetic 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 (MHC) 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. PMCID: PMC2780864 PMID: 19720792 [PubMed - indexed for MEDLINE] PUBMED: 19720792
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