RGD Reference Report - Genetic modifiers of Leprfa associated with variability in insulin production and susceptibility to NIDDM. - Rat Genome Database

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Genetic modifiers of Leprfa associated with variability in insulin production and susceptibility to NIDDM.

Authors: Chung, WK  Zheng, M  Chua, M  Kershaw, E  Power-Kehoe, L  Tsuji, M  Wu-Peng, XS  Williams, J  Chua SC, JR  Leibel, RL 
Citation: Chung WK, etal., Genomics 1997 May 1;41(3):332-44
RGD ID: 61083
Pubmed: PMID:9169130   (View Abstract at PubMed)
DOI: DOI:10.1006/geno.1997.4672   (Journal Full-text)

In an attempt to identify the genetic basis for susceptibility to non-insulin-dependent diabetes mellitus within the context of obesity, we generated 401 genetically obese Leprfa/Leprfa F2 WKY13M intercross rats that demonstrated wide variation in multiple phenotypic measures related to diabetes, including plasma glucose concentration, percentage of glycosylated hemoglobin, plasma insulin concentration, and pancreatic islet morphology. Using selective genotyping genome scanning approaches, we have identified three quantitative trait loci (QTLs) on Chr. 1 (LOD 7.1 for pancreatic morpholology), Chr. 12 (LOD 5.1 for body mass index and LOD 3.4 for plasma glucose concentration), and Chr. 16 (P < 0.001 for genotype effect on plasma glucose concentration). The obese F2 progeny demonstrated sexual dimorphism for these traits, with increased diabetes susceptibility in the males appearing at approximately 6 weeks of age, as sexual maturation occurred. For each of the QTLs, the linked phenotypes demonstrated sexual dimorphism (more severe affection in males). The QTL on Chr. 1 maps to a region vicinal to that previously linked to adiposity in studies of diabetes susceptibility in the nonobese Goto-Kakizaki rat, which is genetically closely related to the Wistar counterstrain we employed. Several candidate genes, including tubby (tub), multigenic obesity 1 (Mob1), adult obesity and diabetes (Ad), and insulin-like growth factor-2 (Igf2), map to murine regions homologous to the QTL region identified on rat Chr. 1.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
type 2 diabetes mellitus  IDA 61083; 61083 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
abnormal pancreatic islet morphology  QTM 61083; 61083 RGD 
increased body weight  QTM 61083; 61083 RGD 
increased circulating glucose level  QTM 61083; 61083 RGD 
Objects Annotated

QTLs
Bw120  (Body weight QTL 120)
Niddm4  (Non-insulin dependent diabetes mellitus QTL 4)
Niddm6  (Non-insulin dependent diabetes mellitus QTL 6)
Pancm1  (Pancreatic morphology QTL 1)

Strains
13M  (NA)
WKY  (NA)

Objects referenced in this article
Marker D16Mit2 D16Mit2 Rattus norvegicus
Marker D12Mit5 D12Mit5 Rattus norvegicus
Marker D12Mgh6 D12Mgh6 Rattus norvegicus
Marker D1Wox10 D1Wox10 Rattus norvegicus
Gene Spn sialophorin Rattus norvegicus

Additional Information