RGD Reference Report - Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

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Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.
Authors:	Watanabe, TK Okuno, S Ono, T Yamasaki, Y Oga, K Mizoguchi-Miyakita, A Miyao, H Suzuki, M Momota, H Goto, Y Shinomiya, H Hishigaki, H Hayashi, I Asai, T Wakitani, S Takagi, T Nakamura, Y Tanigami, A
Citation:	Watanabe TK, etal., Clin Exp Pharmacol Physiol 2001 Jan-Feb;28(1-2):28-42.
RGD ID:	619683
Pubmed:	PMID:11153534 (View Abstract at PubMed)
1. Whole-genome scans have identified Dmo1 as a major quantitative trait locus for dyslipidaemia and obesity in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. 2. We have produced congenic rats for the Dmo1 locus through successive back-cross breeding with diabetic OLETF rats. Marker-assisted speed congenic protocols were applied to efficiently transfer chromosomal segments from non-diabetic Brown Norway (BN) rats into the OLETF background. 3. In the fourth generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. 4. We have concluded that Dmo1 primarily affects lipid homeostasis, obesity control and/or glucose homeostasis at fasting and is secondarily involved in glucose homeostasis after loading. 5. The results of the present study show that single-allele correction of a genetic defect of the Dmo1 locus can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Niddm58	Rat	Insulin Resistance		IAGP			RGD
Niddm58	Rat	obesity		IAGP			RGD
Niddm58	Rat	type 2 diabetes mellitus		IAGP			RGD

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Mammalian Phenotype

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Niddm58	Rat	decreased body weight		IDA			RGD
Niddm58	Rat	decreased circulating insulin level		IAGP			RGD
Niddm58	Rat	decreased circulating triglyceride level		IDA			RGD
Niddm58	Rat	decreased total body fat amount		IDA			RGD
Niddm58	Rat	improved glucose tolerance		IAGP			RGD

Objects Annotated

QTLs

Niddm58 (Non-insulin dependent diabetes mellitus QTL 58)

Strains

OLETF.BN-(D1Rat76-D1Rat459)/Got (NA)

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Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

Mammalian Phenotype