HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Appendix Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Blankenhorn, E. P. Articles by Mordes, J. P. Search for Related Content PubMed PubMed Citation Articles by Blankenhorn, E. P. Articles by Mordes, J. P. Social Bookmarking                What's this?

The Rat Diabetes Susceptibility Locus Iddm4 and at Least One Additional Gene Are Required for Autoimmune Diabetes Induced by Viral Infection

¹ Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, Pennsylvania
² Department of Medicine, University of Massachusetts, Worcester, Massachusetts

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–ß-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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. H. Wallis, K. Wang, D. Dabrowski, L. Marandi, T. Ning, E. Hsieh, A. D. Paterson, J. P. Mordes, E. P. Blankenhorn, and P. Poussier A Novel Susceptibility Locus on Rat Chromosome 8 Affects Spontaneous but Not Experimentally Induced Type 1 Diabetes Diabetes, June 1, 2007; 56(6): 1731 - 1736. [Abstract] [Full Text] [PDF]

				D. Zipris, E. Lien, A. Nair, J. X. Xie, D. L. Greiner, J. P. Mordes, and A. A. Rossini TLR9-Signaling Pathways Are Involved in Kilham Rat Virus-Induced Autoimmune Diabetes in the Biobreeding Diabetes-Resistant Rat J. Immunol., January 15, 2007; 178(2): 693 - 701. [Abstract] [Full Text] [PDF]

				J. M. Fuller, A. E. Kwitek, T. J. Hawkins, D. H. Moralejo, W. Lu, T. D. Tupling, A. J. MacMurray, G. Borchardt, M. Hasinoff, and A. Lernmark Introgression of F344 Rat Genomic DNA on BB Rat Chromosome 4 Generates Diabetes-Resistant Lymphopenic BB Rats Diabetes, December 1, 2006; 55(12): 3351 - 3357. [Abstract] [Full Text] [PDF]