Commonalities of genetic resistance to spontaneous autoimmune and free radical--mediated diabetes.

Free Radical Biology & Medicine
Jing ChenClayton E Mathews

Abstract

ALR/Lt, a NOD-related mouse strain, was selected for resistance to alloxan free radical-mediated diabetes (ALD). Despite extensive genomic identity with NOD (>70%), ALR mice display strong resistance to autoimmune type 1 diabetes (T1D) due to both an unusual elevation in systemic antioxidant defenses and a reduction in cellular ROS production that extends to the beta cell level. Reciprocal backcross to NOD previously linked the ALR-derived T1D resistance to Chr. 3, 8, and 17 as well as to the ALR mt-Nd2(a) allele encoded by the mitochondrial genome (mtDNA). To determine whether any of the ALR-derived loci protecting against T1D also protected against ALD, 296 six-week-old F2 mice from reciprocal outcrosses were alloxan-treated and assessed for diabetes onset, and a genome-wide scan (GWS) was conducted. GWS linked mt-Nd2 as well as three nuclear loci with alloxan-induced diabetes. A dominant ALR-derived ALD resistance locus on Chr. 8 colocalized with the ALR-derived T1D resistance locus identified in the previous backcross analysis. In contrast, whereas ALR contributed a novel T1D resistance locus on Chr. 3 marked by Susp, a more proximal ALR-derived region marked by Il-2 contributed ALD susceptibility, not resistance. In additi...Continue Reading

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Citations

May 6, 2010·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Sivarajan KumarasamyBina Joe
Jan 1, 2012·The Review of Diabetic Studies : RDS·John P DriverClayton E Mathews
Sep 5, 2014·Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis·Mo-Chao XiaoYe Tian
Nov 8, 2014·Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis·Peng ZhangBen-Kang Shi
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Jan 6, 2009·Annals of the New York Academy of Sciences·Jing ChenClayton E Mathews
Nov 10, 2011·Diabetes/metabolism Research and Reviews·Jing ChenClayton E Mathews
Dec 17, 2014·Neuroscience Letters·Aaron M GusdonSheng-di Chen
Jan 4, 2018·Antioxidants & Redox Signaling·Jing ChenClayton E Mathews
Aug 22, 2017·Frontiers in Endocrinology·Undurti N Das
Oct 1, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hubert M TseClayton E Mathews

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