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

Published online by Cambridge University Press:  08 June 2001

SHIRO OKUNO ,
TAKESHI K. WATANABE ,
TOSHIHIDE ONO ,
KEIKO OGA ,
AYAKO MIZOGUCHI-MIYAKITA ,
YUKI YAMASAKI ,
YOSHIHIRO GOTO ,
HIROICHI SHINOMIYA ,
HIROSHI MOMOTA  and
HIDEO MIYAO
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SHIRO OKUNO
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
TAKESHI K. WATANABE
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
TOSHIHIDE ONO
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
KEIKO OGA
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
AYAKO MIZOGUCHI-MIYAKITA
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
YUKI YAMASAKI
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
YOSHIHIRO GOTO
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
HIROICHI SHINOMIYA
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
HIROSHI MOMOTA
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
HIDEO MIYAO
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
ISAMU HAYASHI
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
TOSHIHIRO ASAI
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
MIKIO SUZUKI
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
YOSUKE HARADA
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
HARETSUGU HISHIGAKI
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
SHIGEYUKI WAKITANI
Affiliation:
Department of Orthopaedic Surgery, Osaka-Minami National Hospital, 2-1 Kidohigashi-machi, Kawachinagano, Osaka 586-8521, Japan
TOSHIHISA TAKAGI
Affiliation:
Laboratory of Genome Database, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo 108-8639, Japan
YUSUKE NAKAMURA
Affiliation:
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai Minato-ku, Tokyo 108-8639, Japan
AKIRA TANIGAMI
Affiliation:
Otsuka GEN Research Institute, Otsuka Pharmaceutical Co., Ltd, 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan
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Abstract

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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.

Type
Research Paper
Information
Genetics Research , Volume 77 , Issue 2 , February 2001 , pp. 183 - 190
Copyright
© 2001 Cambridge University Press