Nature Genetics
30, 151 - 157 (2002)
Published online: 14 January 2002; | doi:10.1038/ng814
Angptl3 regulates lipid metabolism in miceRyuta Koishi1, 5, Yosuke Ando2, 5, Mitsuru Ono1, 5, Mitsuru Shimamura1, Hiroaki Yasumo1, Toshihiko Fujiwara3, Hiroyoshi Horikoshi4
& Hidehiko Furukawa11
Biomedical Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. 2
Medicinal Safety Research Laboratories, Sankyo Co., Ltd., 717, Horikoshi, Fukuroi, Shizuoka-ken, 437-0065, Japan. 3
Pharmacology & Molecular Biology Research Laboratories, Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. 4
Sankyo Pharma Research Institute, 4250 Executive Square, Suite 420, La Jolla, California 92037, USA. 5
These authors contributed equally to this work.
Correspondence should be addressed to Ryuta Koishi koishi@shina.sankyo.co.jpThe KK obese mouse is moderately obese and has abnormally high levels of plasma insulin (hyperinsulinemia), glucose (hyperglycemia) and lipids (hyperlipidemia). In one strain (KK/San), we observed abnormally low plasma lipid levels (hypolipidemia). This mutant phenotype is inherited recessively as a mendelian trait. Here we report the mapping of the hypolipidemia (hypl) locus to the middle of chromosome 4 and positional cloning of the autosomal recessive mutation responsible for the hypolipidemia. The hypl locus encodes a unique angiopoietin-like lipoprotein modulator, which we named Allm1. It is identical to angiopoietin-like protein 3, encoded by Angptl3, and has a highly conserved counterpart in humans. Overexpression of Angptl3 or intravenous injection of the purified protein in KK/San mice elicited an increase in circulating plasma lipid levels. This increase was also observed in C57BL/6J normal mice. Taken together, these data suggest that Angptl3 regulates lipid metabolism in animals.
|
