Characterization of transgenic rats constitutively expressing vitamin D-24-hydroxylase gene

被引：52

作者：

Kasuga, H

Hosogane, N

Matsuoka, K

Mori, I

Sakura, Y

Shimakawa, K

Shinki, T

Suda, T

Taketomi, S

机构：

[1] Takeda Chem Ind Ltd, Div Pharmaceut Res, Yodokawa Ku, Osaka 5328686, Japan

[2] Showa Univ, Sch Dent, Dept Oral Biochem, Shinagawa Ku, Tokyo 1428555, Japan

[3] Keio Univ, Sch Med, Dept Orthopaed Surg, Shinjuku Ku, Tokyo 1608582, Japan

[4] Saitama Med Sch, Res Ctr Genom Med, Div Pathophysiol, Hidaka, Saitama 3501241, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2002年 / 297卷 / 05期

关键词：

vitamin D; 24-hydroxylase(CYP24); 1; alpha; 25(OH)(2)D-3; 24,25(OH)(2)D-3; transgenic rat; alburninuria; hyperlipidemia; cholesterol; triglyceride;

D O I：

10.1016/S0006-291X(02)02254-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Vitamin D-24-hydroxylase (CYP24) is one of the enzymes responsible for vitamin D metabolism. CYP24 catalyzes the conversion of 25-hydroxyvitamin D-3 [25(OH)D-3] to 24,25-dihydroxyvitamin D-3 [24,25(OH)(2)D-3] in the kidney. CYP24 is also involved in the breakdown of 1alpha,25-dihydroxyvitamin D-3 [1alpha,25(OH)(2)D-3], the active form of vitamin D3. In this study, we generated transgenic (Tg) rats constitutively expressing CYP24 gene to investigate the biological role of CYP24 in vivo. Surprisingly, the Tg rats showed a significantly low level of plasma 24,25(OH)(2)D-3. Furthermore, the Tg rats developed albuminuria and hyperlipidemia shortly after weaning. The plasma lipid profile revealed that all lipoprotein fractions were elevated in the Tg rats. Also, the Tg rats showed atherosclerotic lesions in the aorta, which greatly progressed with high-fat and high-cholesterol feeding. These unexpected results suggest that CYP24 is involved in functions other than the regulation of vitamin D metabolism. (C) 2002 Elsevier Science (USA). All rights reserved.

引用

页码：1332 / 1338

页数：7

共 39 条

[1] Mouse vitamin D-24-hydroxylase: Molecular cloning, tissue distribution, and transcriptional regulation by 1 alpha,25-dihydroxyvitamin D-3 [J].