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Quantitative Trait Loci For Lipid Metabolism In The Study Of Oletf × (Oletf × Fischer 344) Backcross Rats
Author(s) -
Yamasaki Yuki,
Watanabe Takeshi K,
Okuno Shiro,
Ono Toshihide,
Oga Keiko,
MizoguchiMiyakita Ayako,
Goto Yoshihiro,
Shinomiya Hiroichi,
Momota Hiroshi,
Miyao Hideo,
Hayashi Isamu,
Asai Toshihiro,
Suzuki Mikio,
Harada Yosuke,
Hishigaki Haretsugu,
Wakitani Shigeyuki,
Takagi Toshihisa,
Nakamura Yusuke,
Tanigami Akira
Publication year - 2000
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.1440-1681.2000.03353.x
Subject(s) - medicine , endocrinology , quantitative trait locus , diabetes mellitus , triglyceride , obesity , biology , type 2 diabetes , backcrossing , leptin , cholesterol , locus (genetics) , hypertriglyceridemia , gene , genetics
SUMMARY 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 × (OLETF × 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 × 10 –6 at D1Rat90 ) and total cholesterol ( P = 1.16 × 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.