| Project/Area Number |
12835005
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Institution | Osaka University |
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Principal Investigator |
YAMASHITA Shizuya Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (60243242)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Ken-ichi Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30332737)
SAKAI Naohiko Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80294073)
TOMIYAMA Yoshiaki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (80252667)
西田 誠 大阪大学, 医学部・附属病院, 医員
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | CD36 / Atherosclerosis / Knockout mice / Oxidized LDL / 受容体 / 粥状動脈硬化 / 長鎖脂肪酸 / スカベンジャー受容体 |
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| Research Abstract |
CD36 is a membrane glycoprotein expressed on platelets, monocytes/macrophages and adipose tissues. CD36 belongs to the class B scavenger receptor family. We found patients with CD36 deficiency in 1990 and analyzed the pathophysiology of these patients.
We have identified 3 novel mutations in the CD36 gene and reported that macrophages from CD36-deficient patients showed a reduced capacity to bind oxidized LDL and were resistant to foam cell formation. Thus, CD36 may be one of the important receptors for oxidized LDL. Furthermore, we have found that CD36 is also expressed in cardiac muscles of CD36-positive subjects, but not in those of CD36-deficient patients.
The deficiency of CD36 may lead to the high frequency of cardiomyopathy in these patients.
Little has been known as to the in vivo effect of CD36 deficiency. We found that CD36-deficient patients are accompanied by insulin resistance, which is a common phenotype of multiple risk factor syndrome. In the current study, we have used genetic engineering techniques to establish CD36 knockout mice and elucidate the role of CD36 in the pathogenesis of atherosclerosis.
We have established chimera mice and have obtained homozygotes of CD36 knockout mice. We have performed a backcross breeding and are currently trying to see the changes of serum lipids, glucose metabolism and the presence or absence of insulin resistance in these mice. We will finally examine the susceptibility of CD36 knockout mice to atherosclerosis.
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