RGD Reference Report - Enhanced insulin secretion and cholesterol metabolism in congenic strains of the spontaneously diabetic (Type 2) Goto Kakizaki rat are controlled by independent genetic loci in rat chromosome 8. - Rat Genome Database

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Enhanced insulin secretion and cholesterol metabolism in congenic strains of the spontaneously diabetic (Type 2) Goto Kakizaki rat are controlled by independent genetic loci in rat chromosome 8.

Authors: Wallis, RH  Wallace, KJ  Collins, SC  McAteer, M  Argoud, K  Bihoreau, MT  Kaisaki, PJ  Gauguier, D 
Citation: Wallis RH, etal., Diabetologia 2004 Jun;47(6):1096-106. Epub 2004 May 26.
RGD ID: 1300044
Pubmed: PMID:15164172   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-004-1416-5   (Journal Full-text)

AIMS/HYPOTHESIS. Genetic investigations in the spontaneously diabetic (Type 2) Goto Kakizaki (GK) rat have identified quantitative trait loci (QTL) for diabetes-related phenotypes. The aims of this study were to refine the chromosomal mapping of a QTL ( Nidd/gk5) identified in chromosome 8 of the GK rat and to define a pathophysiological profile of GK gene variants underlying the QTL effects in congenics. METHODS. Genetic linkage analysis was carried out with chromosome 8 markers genotyped in a GKxBN F2 intercross previously used to map diabetes QTL. Two congenic strains were designed to contain GK haplotypes in the region of Nidd/gk5 transferred onto a Brown Norway (BN) genetic background, and a broad spectrum of diabetes phenotypes were characterised in the animals. RESULTS. Results from QTL mapping suggest that variations in glucose-stimulated insulin secretion in vivo, and in body weight are controlled by different chromosome 8 loci (LOD3.53; p=0.0004 and LOD4.19; p=0.00007, respectively). Extensive physiological screening in male and female congenics at 12 and 24 weeks revealed the existence of GK variants at the locus Nidd/gk5, independently responsible for significantly enhanced insulin secretion and increased levels of plasma triglycerides, phospholipids and HDL, LDL and total cholesterol. Sequence polymorphisms detected between the BN and GK strains in genes encoding ApoAI, AIV, CIII and Lipc do not account for these effects. CONCLUSIONS/INTERPRETATION. We refined the localisation of the QTL Nidd/gk5 and its pathophysiological characteristics in congenic strains derived for the locus. These congenic strains provide novel models for testing the contribution of a subset of GK alleles on diabetes phenotypes and for identifying diabetes susceptibility genes.



Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype

Objects Annotated

QTLs
Bw23  (Body weight QTL 23)
Niddm61  (Non-insulin dependent diabetes mellitus QTL 61)

Strains
BN  (BN)
GK/KyoSwe  (Goto Kakizaki)

Objects referenced in this article
Marker D8Got302 D8Got302 Rattus norvegicus
Strain BN.GK-(D8Got302-D8Got130)/Ox null Rattus norvegicus
Strain BN.GK-(D8Rat29-D8Got130)/Ox null Rattus norvegicus

Additional Information