RGD Reference Report - Substitution of Dmo1 with normal alleles results in decreased manifestation of diabetes in OLETF rats. - Rat Genome Database

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Substitution of Dmo1 with normal alleles results in decreased manifestation of diabetes in OLETF rats.

Authors: Okuno, S  Kondo, M  Yamasaki, Y  Miyao, H  Ono, T  Iwanaga, T  Omori, K  Okano, M  Suzuki, M  Momota, H  Hishigaki, H  Hayashi, I  Goto, Y  Shinomiya, H  Harada, Y  Hirashima, T  Kanemoto, N  Asai, T  Wakitani, S  Takagi, T  Nakamura, Y  Tanigami, A  Watanabe, TK 
Citation: Okuno S, etal., Diabetes Obes Metab 2002 Sep;4(5):309-18.
RGD ID: 734465
Pubmed: PMID:12190994   (View Abstract at PubMed)

AIM: Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes in the Otsuka Long Evans Tokushima Fatty (OLETF) rat strain. To evaluate possible metabolic and pathological improvements generated by correction of the Dmo1 genetic pathway, we produced congenic lines, in which both OLETF Dmo1 alleles are replaced by the F344-derived genome. METHODS: Congenic animals were produced by introgressing F344-derived Dmo1 alleles into the OLETF rat. Congenic animals of the fourth generation (BC4) were intercrossed to obtain F1 animals (BC4:F1). Animals of the next generation, BC4:F2, were used for this study. We used 23 BC4:F2 males harbouring homozygous replacement of the OLETF Dmo1 region with the F344-derived genome. Seven animals with OLETF-derived Dmo1 alleles were used as controls. RESULTS: Dmo1-F344/F344 congenic rats showed significant decreases in body weight, abdominal fat weight, serum triacylglycerols, total cholesterol, food consumption and blood glucose after glucose loading (13%, 39%, 45%, 27%, 18% and 27% respectively; p < 0.05) compared with Dmo1-OLETF/OLETF animals. Furthermore, histopathological analysis of the kidney showed that mesangial sclerosis, hyalin deposits and deposition of PAS-positive substance were significantly lower in Dmo1-F344/F344 animals (p < 0.05). CONCLUSION: Improvements in metabolic parameters and histopathological scores show that correction of the Dmo1 genetic pathway in the diabetic and mildly obese OLETF rat strain produces wide-ranging therapeutic effects. Thus, this pathway might represent a new drug target also applicable to humans.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Niddm59Ratobesity  IAGP  RGD 
Niddm59Rattype 2 diabetes mellitus  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased abdominal fat pad weight  IAGP compared to OLETF/GotRGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased body length  IAGP compared to OLETF/GotRGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased body mass index  IAGP compared to OLETF/GotRGD 
Niddm59Ratdecreased body weight  IDA  RGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased body weight  IAGP compared to OLETF/GotRGD 
Niddm59Ratdecreased circulating cholesterol level  IDA  RGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased circulating cholesterol level  IAGP compared to OLETF/GotRGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased circulating triglyceride level  IAGP compared to OLETF/GotRGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased food intake  IAGP compared to OLETF/GotRGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased glycosylated hemoglobin level  IAGP compared to OLETF/GotRGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased liver weight  IAGP compared to OLETF/GotRGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatdecreased mesenteric fat pad weight  IAGP compared to OLETF/GotRGD 
Niddm59Ratdecreased total body fat amount  IDA  RGD 
Niddm59Ratdecreased triglyceride level  IDA  RGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatimproved glucose tolerance inducedIAGPglucose solutioncompared to OLETF/GotRGD 
OLETF.F344-(D1Rat306-D1Rat461)/GotRatincreased brain weight  IAGP compared to OLETF/GotRGD 
Objects Annotated

QTLs
Niddm59  (Non-insulin dependent diabetes mellitus QTL 59)


Additional Information