Single-Allele Correction Of The Dmo1 Locus In Congenic Animals Substantially Attenuates Obesity, Dyslipidaemia And Diabetes Phenotypes Of The Oletf Rat

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‐assi...

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Published in:Clinical and experimental pharmacology & physiology 2001-01, Vol.28 (1-2), p.28-42
Main Authors: Watanabe, Takeshi K, Okuno, Shiro, Ono, Toshihide, Yamasaki, Yuki, Oga, Keiko, Mizoguchi-Miyakita, Ayako, Miyao, Hideo, Suzuki, Mikio, Momota, Hiroshi, Goto, Yoshihiro, Shinomiya, Hiroichi, Hishigaki, Haretsugu, Hayashi, Isamu, Asai, Toshihiro, Wakitani, Shigeyuki, Takagi, Toshihisa, Nakamura, Yusuke, Tanigami, Akira
Format: Article
Language:English
Subjects:
Alleles
Animals
Animals, Congenic
Blood Glucose - genetics
Body Weight - genetics
Chromosome Mapping - methods
congenic
diabetes
Diabetes Mellitus, Type 2 - genetics
Dmo1
dyslipidaemia
genetic analysis
Hyperlipidemias - genetics
Insulin - blood
Male
obesity
Obesity - genetics
Otsuka Long Evans Tokushima Fatty rat
Phenotype
quantitative trait locus
Rats
Rats, Long-Evans
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Summary: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.
ISSN:0305-1870
1440-1681
DOI:10.1046/j.1440-1681.2001.03391.x