International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


K F. Fujimoto
Sankyo Co., Ltd., Medicinal Safety Research Laboratories

1) Ando Y, 1) Ogata S, 2) Koishi R, 2) Yasumo H, 1) Yamauchi S, 1) Takeshita S, 1) Kanbori M, 2) Furukawa H
1) Medicinal Safety Research Laboratories, 2) Biomedical Research Laboratories, Sankyo Co., Ltd

Angiopoietin-1 and Angiopoietin-2 bind a tyrosine kinase receptor, Tie-2, and regulate vascular formation. Angiopoietins contain a signal peptide, fibrinogen-like domain and coiled-coil domain. Recently, novel subfamilies of Angiopoietin, which contain the characteristic domains, were discovered. We reported that an insertional mutation in the Angiopoietin-like 3 (Angptl3) gene caused hypolipidemia in KK diabetic mice, although the Angptl3 mRNA was still detectable by Northern analysis. We next, generated Angptl3-deficient (Angptl3-/-) mice, in which the Angptl3 gene was no longer expressed, and investigated the phenotype. Angptl3-/- mice showed significantly low plasma lipid concentrations, especially triglycerides, similar to hypolipidemic KK diabetic mice. No pathologoical abnormalities were observed in Angptl3-/- mice fed normal and high-fat diets. Lipid load and Triton injection studies showed that the low level of plasma triglyceride concentration was mainly due to an increase in plasma triglyceride lypolisis.

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