title: Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain.
abstract: Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using marker-assisted speed congenic protocols, enforced by selective removal of other QTL regions (QTL-marker-assisted counterselection), to efficiently transfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into the OLETF background. In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. We conclude that single-allele correction of an impaired genetic pathway 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, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Okuno
authors.forename: T K
authors.initials: TK
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Ono
authors.forename: K
authors.initials: K
authors.lastname: Oga
authors.forename: A
authors.initials: A
authors.lastname: Mizoguchi-Miyakita
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
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: Momota
authors.forename: H
authors.initials: H
authors.lastname: Miyao
authors.forename: I
authors.initials: I
authors.lastname: Hayashi
authors.forename: T
authors.initials: T
authors.lastname: Asai
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Hishigaki
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; D001786:Blood Glucose / Q000378:metabolism; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006943:Hyperglycemia / Q000235:genetics*; D006949:Hyperlipidemias / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D011922:Rats, Mutant Strains
chemical_list: D001786:Blood Glucose; D005819:Genetic Markers