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Diubiquitin (Ubd) is a susceptibility gene for virus-triggered autoimmune diabetes in rats
Journal article   Open access   Peer reviewed

Diubiquitin (Ubd) is a susceptibility gene for virus-triggered autoimmune diabetes in rats

Laura Cort, Michael Habib, Ryan A. Eberwine, Martin J. Hessner, John P. Mordes and Elizabeth P. Blankenhorn
Genes and immunity, v 15(3)
01 Jan 2014
DOI: https://doi.org/10.1038/gene.2013.72
PMID: 24452267
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc4260472View
Accepted (AM)Open Access (License Unspecified),  Open
url
https://doi.org/10.1038/gene.2013.72View
Published, Version of Record (VoR) Open

Abstract

Autoimmune diabetes rat model susceptibility genes virus-induced
Genetic studies of type 1 diabetes (T1D) have been advanced by comparative analysis of multiple susceptible and resistant rat strains with a permissive class II MHC haplotype, RT1 u . LEW.1WR1 (but not resistant LEW.1W or WF) rats are susceptible to T1D induced by a TLR3 agonist (poly I:C) followed by infection with parvovirus. We have mapped genetic loci for virus-induced T1D susceptibility, identifying a major susceptibility locus ( Iddm37 ) near the MHC. Iddm37 homologues on mouse and human chromosomes are also diabetes-linked. We report that a major effect gene within Iddm37 is diubiquitin (Ubd) . Gene expression profiling of pancreatic lymph nodes in susceptible and resistant rats during disease induction showed differences in Ubd transcript abundance. The LEW.1WR1 Ubd promoter allele leads to higher inducible levels of UBD than that of LEW.1W or WF. Using zinc finger nucleases (ZFN), we deleted a segment of the LEW.1WR1 Ubd gene and eliminated its expression. UBD-deficient rats show substantially reduced diabetes after viral infection. Complementation studies show that there may be another diabetes gene in addition to Ubd in the Iddm37 interval. These data prove that Ubd is a diabetes susceptibility gene, providing insight into the interplay of multiple genes and environmental factors in T1D susceptibility.

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16 Record Views
15 citations in Web of Science
14 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Genetics & Heredity
Immunology
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