RESEARCH ARTICLE


Genetics of the Spontaneously Diabetic Torii Rat



Norihide Yokoi1, *, Masanori Fuse1, Susumu Seino1, 2
Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.

Article Information


Identifiers and Pagination:

Year: 2011
Volume: 4
First Page: 21
Last Page: 25
Publisher Id: TODIAJ-4-21
DOI: 10.2174/1876524601104010021

Article History:

Received Date: 18/08/2010
Revision Received Date: 19/10/2010
Acceptance Date: 16/01/2011
Electronic publication date: 28/3/2011
Collection year: 2011

© Yokoi et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.E-mail: yokoi@med.kobe-u.ac.jp


Abstract

The Spontaneously Diabetic Torii (SDT) rat has recently been established as a novel model of nonobese type 2 diabetes. SDT rats exhibit inflammation and fibrosis in and around the islets during development of the disease. To clarify the genetic basis of the disease, we previously performed quantitative trait locus (QTL) analysis of glucose tolerance at 20 weeks of age using backcrossed progeny produced from the (BN􀀁SDT)F1􀀁SDT cross. The analysis identified three major QTLs (Gisdt1, Gisdt2, and Gisdt3) on rat chromosomes 1, 2, and X, respectively. To examine genetic factors for diabetes, glucose tolerance, islet inflammation, and fibrosis in the SDT rat, we also performed genetic analysis of these traits at 60 weeks of age using intercrossed progeny produced from the (F344􀀁SDT)F2 cross. Genetic analysis of diabetes identified a major locus, Dmsdt1, on chromosome 3. QTL analysis of blood glucose levels revealed, in addition to Dmsdt1, three other loci (Dmsdt2, Dmsdt3, and Dmsdt4) on chromosome 8, 13, and 14, respectively. Analysis of a congenic strain for Dmsdt1 (F344.SDT-Dmsdt1) indicates that the dominantly acting SDT allele induces islet inflammation and fibrosis. These data clearly demonstrate that development of diabetes in the SDT rat is controlled by the combination of several QTLs with considerable effects. Identification of the genes responsible would provide greater understanding of the pathogenesis and pathophysiology of diabetes.