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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
Author(s) -
Watanabe Takeshi K,
Okuno Shiro,
Ono Toshihide,
Yamasaki Yuki,
Oga Keiko,
MizoguchiMiyakita 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
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03391.x
Subject(s) - congenic , endocrinology , locus (genetics) , allele , medicine , glucose homeostasis , obesity , biology , quantitative trait locus , homeostasis , diabetes mellitus , phenotype , insulin resistance , genetics , gene
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.