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.
Pubmed: (View Article at PubMed) PMID:11153534

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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Created: 2002-08-05
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