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Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain

  • SHIRO OKUNO (a1), TAKESHI K. WATANABE (a1), TOSHIHIDE ONO (a1), KEIKO OGA (a1), AYAKO MIZOGUCHI-MIYAKITA (a1), YUKI YAMASAKI (a1), YOSHIHIRO GOTO (a1), HIROICHI SHINOMIYA (a1), HIROSHI MOMOTA (a1), HIDEO MIYAO (a1), ISAMU HAYASHI (a1), TOSHIHIRO ASAI (a1), MIKIO SUZUKI (a1), YOSUKE HARADA (a1), HARETSUGU HISHIGAKI (a1), SHIGEYUKI WAKITANI (a2), TOSHIHISA TAKAGI (a3), YUSUKE NAKAMURA (a4) and AKIRA TANIGAMI (a1)...

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.

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      Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain
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Copyright

Corresponding author

Corresponding author. Tel: +81 886 65 2888. Fax: +81 886 37 1035. e-mail: watanabe@otsuka.gr.jp

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