RGD Reference Report - Single diabetic QTL derived from OLETF rat is a sufficient agent for severe diabetic phenotype in combination with leptin-signaling deficiency. - Rat Genome Database

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Single diabetic QTL derived from OLETF rat is a sufficient agent for severe diabetic phenotype in combination with leptin-signaling deficiency.

Authors: Kose, H  Yamada, T  Matsumoto, K 
Citation: Kose H, etal., Exp Diabetes Res. 2012;2012:858121. doi: 10.1155/2012/858121. Epub 2012 Dec 5.
RGD ID: 7394771
Pubmed: PMID:23304119   (View Abstract at PubMed)
PMCID: PMC3529458   (View Article at PubMed Central)
DOI: DOI:10.1155/2012/858121   (Journal Full-text)

Obesity has been considered one of the leading causative agents for diseases such as type 2 diabetes, stroke, and heart attack. Due to their complex etiology, establishing a useful animal model is increasingly crucial for better molecular understanding of how obesity influences on disease development. OLETF rat is a spontaneous model of type 2 diabetes. We mapped 14 hyperglycemia QTLs in the genome of the OLETF rat and subsequently generated a panel of congenic strains each possessing OB-R mutation in F344 genetic background. Here we show that one of the loci, Nidd2/of, is highly responsive to obesity. When leptin receptor mutation is introgressed into the Nidd2/of congenic strain, the rat showed hyperglycemia equivalent to that of the parental OLETF rat. This suggests that the Nidd2/of locus has a strong genetic interaction with leptin signaling pathway. Furthermore, when another hyperglycemia QTL Nidd1/of is additionally combined, the strain developed overt diabetes. A single QTL dissected out in spontaneous model normally exerts only mild effect on the quantitative trait, which makes it difficult to clone the gene. Our new model may help not only to identify the causative gene but also to investigate how obesity interacts with a QTL to regulate diabetic traits.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
F344.ZUC-Leprfa/TjRathyperglycemia  IAGP at 15 wks of ageRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
F344.ZUC-Leprfa/TjRatincreased circulating glucose level  IAGP at 15 wks of ageRGD 
Objects Annotated

Strains
F344.ZUC-Leprfa/Tj  (NA)

Objects referenced in this article
Strain (F344.OLETF-(D14Rat23-D14Rat12)(D14Rat8-D14Rat26)/2Tj x F344.Cg-Leprfa(D7Mgh16-D7Mgh20))F1 null Rattus norvegicus
Strain F344.Cg-Leprfa(D7Rat18-D7Mit2)(D14Rat23-D14Rat12)/Tj null Rattus norvegicus
Strain F344.ZUC-(Leprfa)(D7Rat16-D7Mgh20)/Tj null Rattus norvegicus
Strain F344.ZUC-Leprfa(D14Rat23-D14Rat12)/Tj null Rattus norvegicus

Additional Information