title: Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.
abstract: 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.
authors.affiliation: Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan. watanabe@otsuka.gr.jp
authors.forename: T K
authors.initials: TK
authors.lastname: Watanabe
authors.forename: S
authors.initials: S
authors.lastname: Okuno
authors.forename: T
authors.initials: T
authors.lastname: Ono
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: K
authors.initials: K
authors.lastname: Oga
authors.forename: A
authors.initials: A
authors.lastname: Mizoguchi-Miyakita
authors.forename: H
authors.initials: H
authors.lastname: Miyao
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: H
authors.initials: H
authors.lastname: Momota
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: H
authors.initials: H
authors.lastname: Shinomiya
authors.forename: H
authors.initials: H
authors.lastname: Hishigaki
authors.forename: I
authors.initials: I
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Asai
authors.forename: S
authors.initials: S
authors.lastname: Wakitani
authors.forename: T
authors.initials: T
authors.lastname: Takagi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Tanigami
mesh_terms: D000483:Alleles; D000818:Animals; D020296:Animals, Congenic; D001786:Blood Glucose / Q000235:genetics*; D001835:Body Weight / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D006949:Hyperlipidemias / Q000235:genetics*; D007328:Insulin / Q000097:blood; D008297:Male; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D001786:Blood Glucose; D007328:Insulin