RGD Reference Report - A novel model of obesity-related diabetes: introgression of the Lepr(fa) allele of the Zucker fatty rat into nonobese Spontaneously Diabetic Torii (SDT) rats. - Rat Genome Database

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A novel model of obesity-related diabetes: introgression of the Lepr(fa) allele of the Zucker fatty rat into nonobese Spontaneously Diabetic Torii (SDT) rats.

Authors: Masuyama, T  Katsuda, Y  Shinohara, M 
Citation: Masuyama T, etal., Exp Anim. 2005 Jan;54(1):13-20.
RGD ID: 2314025
Pubmed: PMID:15725677   (View Abstract at PubMed)

An fa allele of the leptin receptor gene (Lepr(fa)) of the Zucker fatty rat was introduced into the genome of the Spontaneously Diabetic Torii (SDT) rat, an inbred model of nonobese type 2 diabetes mellitus, through the 'Speed congenic method'. The newly established congenic strain of a SDT rat for Lepr(fa) was maintained by intercrossing between fa-heterozygous littermates, and the phenotypes related to obesity and diabetes were investigated till 32 wks of age. SDT fa/fa rats of both sexes exhibited obesity, adiposity and insulin resistance associated with hyperphagia from the loss of leptin action. Interestingly, they developed diabetes from 5 wks of age in males and 8 wks in females with the incidences reaching 100% at 16 wks in males and 73% at 32 wks in females. In contrast, heterozygous (+/fa) and wild-type (+/+) rats developed spontaneous nonobese diabetes in males from approximately 20 wks, but not in females, as with the original SDT rats. These results indicate that the fa gene accelerates the onset of diabetes in SDT rats by making adiposity and/or insulin resistance as potent risk factors for development of their diabetes. The SDT.Lepr(fa) congenic rat strain is expected to be a novel model of obesity-related diabetes and could be a useful tool for studies of the genetic backgrounds of diabetes in response to fa-induced obesity.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SDT.Cg-Leprfa/JttRatobesity MODEL: spontaneousIAGP compared to +/+ and +/fa littermatesRGD 
SDT.Cg-Leprfa/JttRattype 2 diabetes mellitus MODEL: spontaneousIAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SDT.Cg-Leprfa/JttRatincreased body mass index  IAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 
SDT.Cg-Leprfa/JttRatincreased body weight  IAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 
SDT.Cg-Leprfa/JttRatincreased circulating glucose level  IAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 
SDT.Cg-Leprfa/JttRatincreased circulating insulin level  IAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 
SDT.Cg-Leprfa/JttRatincreased circulating leptin level  IAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 
SDT.Cg-Leprfa/JttRatincreased food intake  IAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 
SDT.Cg-Leprfa/JttRatincreased interscapular fat pad weight  IAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 
SDT.Cg-Leprfa/JttRatincreased retroperitoneal fat pad weight  IAGP compared to +/+ and +/fa littermates and sexual dimorphism in penetranceRGD 
Objects Annotated

Strains
SDT.Cg-Leprfa/Jtt  (SDT fatty)

Objects referenced in this article
Strain SDT/Jcl null Rattus norvegicus

Additional Information