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Reference: Wallis, RH, Collins, SC, Kaisaki, PJ et al., (2008). Pathophysiological, genetic and gene expression features of a novel rodent model of the cardio-metabolic syndrome. PloS one, 3 (8), Article: e2962.Citable link to this page:

 

Pathophysiological, genetic and gene expression features of a novel rodent model of the cardio-metabolic syndrome.

Abstract: BACKGROUND: Complex etiology and pathogenesis of pathophysiological components of the cardio-metabolic syndrome have been demonstrated in humans and animal models. METHODOLOGY/PRINCIPAL FINDINGS: We have generated extensive physiological, genetic and genome-wide gene expression profiles in a congenic strain of the spontaneously diabetic Goto-Kakizaki (GK) rat containing a large region (110 cM, 170 Mb) of rat chromosome 1 (RNO1), which covers diabetes and obesity quantitative trait loci (QTL), introgressed onto the genetic background of the normoglycaemic Brown Norway (BN) strain. This novel disease model, which by the length of the congenic region closely mirrors the situation of a chromosome substitution strain, exhibits a wide range of abnormalities directly relevant to components of the cardio-metabolic syndrome and diabetes complications, including hyperglycaemia, hyperinsulinaemia, enhanced insulin secretion both in vivo and in vitro, insulin resistance, hypertriglyceridemia and altered pancreatic and renal histological structures. Gene transcription data in kidney, liver, skeletal muscle and white adipose tissue indicate that a disproportionately high number (43-83%) of genes differentially expressed between congenic and BN rats map to the GK genomic interval targeted in the congenic strain, which represents less than 5% of the total length of the rat genome. Genotype analysis of single nucleotide polymorphisms (SNPs) in strains genetically related to the GK highlights clusters of conserved and strain-specific variants in RNO1 that can assist the identification of naturally occurring variants isolated in diabetic and hypertensive strains when different phenotype selection procedures were applied. CONCLUSIONS: Our results emphasize the importance of rat congenic models for defining the impact of genetic variants in well-characterised QTL regions on in vivo pathophysiological features and cis-/trans- regulation of gene expression. The congenic strain reported here provides a novel and sustainable model for investigating the pathogenesis and genetic basis of risks factors for the cardio-metabolic syndrome.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Wellcome Trust Cardiovascular Functional Genomics Initiative   Funder: European Commission   Funder: Swedish Research Council   Funder: Wellcome Trust   Notes:Copyright 2008 Wallis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website: http://www.plos.org

Journal: PloS onesee more from them

Publication Website: http://www.plosone.org

Issue Date: 2008

pages:Article: e2962Identifiers

Urn: uuid:e3be4003-91a1-49f0-a604-0fc1aab3d0c3

Source identifier: 17408

Eissn: 1932-6203

Doi: https://doi.org/10.1371/journal.pone.0002962

Issn: 1932-6203 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Animals Rats, Inbred Strains Rats Islets of Langerhans Disease Models, Animal Body Weight Diabetes Mellitus, Type 2 Hyperglycemia Hyperinsulinism Obesity Arginine Insulin Glucose Blood Glucose Lipids Basal Metabolism Chromosome Mapping Blood Pressure Quantitative Trait Loci Tiny URL: pubs:17408

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Autor: Wallis, RH - institutionUniversity of Oxford - - - Collins, SC - institutionUniversity of Oxford fundingWellcome Prize - - - Kais

Fuente: https://ora.ox.ac.uk/objects/uuid:e3be4003-91a1-49f0-a604-0fc1aab3d0c3



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