Role of Increased ROS Dissipation in Prevention of T1D

Lessons from the ALR Mouse

Authors


Address for correspondence: Clayton E. Mathews, 1600 SW Archer Road, University of Florida, Department of Pathology, Room R4-204, P.O. Box 100275, Gainesville, FL 32610–0275. Voice: +352-392-9803; fax: +352-392-5393. clayton.mathews@pathology.ufl.edu

Abstract

Protection of pancreatic β cells is an approach to prevent autoimmune type 1 diabetes (T1D) and to protect transplanted islets. Reactive oxygen species (ROS) are important mediators of β cell death during the development of T1D. We have examined the role of elevated ROS dissipation in the prevention of T1D using the ALR mouse strain. The selection of ALR, for resistance against alloxan-induced free radical–mediated diabetes, led to a strain of mice with an elevated systemic as well as pancreatic ROS dissipation. Independent genetic mapping studies have identified ALR-derived diabetes protective loci. Conplastic and congenic mouse as well as cell line studies have confirmed the genetic mapping and demonstrated that the elevated ROS dissipation protects ALR β cells from autoimmune destruction. Our data support the hypothesis that elevated ROS dissipation protects β cells against autoimmune destruction and prevents T1D development.

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