title: Quantitative trait loci for lipid metabolism in the study of OLETF x (OLETF x Fischer 344) backcross rats.
abstract: 1. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is a model of type II diabetes with accompanying dyslipidaemia and obesity. 2. To define chromosomal intervals associated with obesity (abdominal fat weight and plasma leptin levels), dyslipidaemia (plasma triglyceride, cholesterol and free fatty acids) and hyperglycaemia (plasma glucose levels), we have performed genome-wide quantitative traits loci (QTL) analyses of 115 male OLETF x (OLETF x Fischer 344) backcross animals at 16 weeks of age. 3. The Diabetes Mellitus OLETF type I (Dmo1) locus on rat chromosome 1 showed statistically significant involvement in elevations of plasma levels of triglycerides (P = 4.87 x 10(-6) at D1Rat90) and total cholesterol (P = 1.16 x 10(-5) at D1Rat306). 4. No other loci produced significant linkage to these observed phenotypes. 5. These analyses have confirmed the importance of Dmo1 in lipid homeostasis at younger ages as well as during overt diabetes, which appears later. Thus, alterations at the Dmo1 locus are a major risk factor for pathogenesis in the strain, a finding that agrees with physiological studies that indicate a role for dyslipidaemia in the type II diabetic syndrome of OLETF rats.
authors.affiliation: Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
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: 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: 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: D000818:Animals; D002784:Cholesterol / Q000097:blood; D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics*; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D019655:Quantitative Trait, Heritable; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D014280:Triglycerides / Q000097:blood
chemical_list: D005819:Genetic Markers; D008055:Lipids; D014280:Triglycerides; D002784:Cholesterol