RGD Reference Report - Pathophysiological, genetic and gene expression features of a novel rodent model of the cardio-metabolic syndrome. - Rat Genome Database

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

Authors: Wallis, RH  Collins, SC  Kaisaki, PJ  Argoud, K  Wilder, SP  Wallace, KJ  Ria, M  Ktorza, A  Rorsman, P  Bihoreau, MT  Gauguier, D 
Citation: Wallis RH, etal., PLoS ONE. 2008 Aug 13;3(8):e2962.
RGD ID: 2300263
Pubmed: PMID:18698428   (View Abstract at PubMed)
PMCID: PMC2500170   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0002962   (Journal Full-text)

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.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BN.GK-(D1Wox18-D1Got254)/OxRatenlarged pancreatic islets  IMP compared to BNRGD 
BN.GK-(D1Wox18-D1Got254)/OxRatincreased body weight  IMP as compared to BN progenitorRGD 
GK/OxRatincreased circulating HDL cholesterol level  IAGP compared to BN.GK-D1Wox18-D1Got254/OxRGD 
GK/OxRatincreased circulating insulin level  IAGP compared to BN.GK-D1Wox18-D1Got254/OxRGD 
GK/OxRatincreased circulating phospholipid level  IAGP compared to BN.GK-D1Wox18-D1Got254/OxRGD 
GK/OxRatincreased circulating VLDL cholesterol level  IAGP compared to BN.GK-D1Wox18-D1Got254/OxRGD 
GK/OxRatincreased fasting circulating glucose level  IAGP compared to BN.GK-D1Wox18-D1Got254/OxRGD 
Objects Annotated


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