IngentaConnect Single-Allele Correction Of The Dmo1 Locus In Congenic Animals Su...

Authors: Watanabe, Takeshi K¹; Okuno, Shiro¹; Ono, Toshihide¹; Yamasaki, Yuki¹; Oga, Keiko¹; Mizoguchi-Miyakita, Ayako¹; Miyao, Hideo¹; Suzuki, Mikio¹; Momota, Hiroshi¹; Goto, Yoshihiro¹; Shinomiya, Hiroichi¹; Hishigaki, Haretsugu¹; Hayashi, Isamu¹; Asai, Toshihiro¹; Wakitani, Shigeyuki; Takagi, Toshihisa; Nakamura, Yusuke; Tanigami, Akira¹

Source: Clinical and Experimental Pharmacology and Physiology, Volume 28, Numbers 1-2, January/February 2001 , pp. 28-42(15)

Publisher: Blackwell Publishing

Abstract:

SUMMARY

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.

Keywords: congenic; diabetes; Dmo1; dyslipidaemia; genetic analysis; obesity; Otsuka Long Evans Tokushima Fatty rat; quantitative trait locus

Document Type: Research article

DOI: 10.1046/j.1440-1681.2001.03391.x

Affiliations: 1: Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima,

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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