1994 Fiscal Year Final Research Report Summary
Application of gene targeting to the study of atherosclerosis
| Project/Area Number |
05404033
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | University of Tokyo |
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Principal Investigator |
YAZAKI Yoshio 3rd.Dept.Int.Med.Univ.of Tokyo, Professor, 医学部(病), 教授 (20101090)
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| Co-Investigator(Kenkyū-buntansha) |
KURIHARA Ukiko 3rd.Dept.Int.Med.Univ.of Tokyo, MD, 医学部(病), 医員
KURIHARA Hiroki 3rd.Dept.Int.Med.Univ.of Tokyo, MD, 医学部(病), 助手 (20221947)
KODAMA Tatsuhiko 3rd.Dept.Int.Med.Univ.of Tokyo, MD,PhD, 医学部(病), 助手 (90170266)
NAGAI Ryozo 3rd.Dept.Int.Med.Univ.of Tokyo, Associate professor, 医学部(病), 助教授 (60207975)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Ahterosclerosis / Endothekial cells / Smooth muscle cell / Macrophage / Gene targeting / Cholesterol / Bllod pressure / Scavenger receptor |
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| Research Abstract |
In order to elucidate the role of multiple genetic factors on the process of atherosclerosis, we used the mouse developmental biological technics, especially gene targeting using homologous recombination in ES cells. We established the endothelin-1 knockout mice, macrophage scavenger receptor knockout mouse, and other gene targeted mice strains in order to analyze the roles of these genes, and the mechanism how endothelial cells, smooth muscle cells and macrophages are involved in the atherogenesis. The heterozygout mice deficient in endothekin-1 indicated the increase of blood pressure. Macrophage obtained from the homozygout for scavenger receptor deficiency indicated the marked decrease in both acetyl-LDL degradation and oxidized LDL degradation. Adding to this, these macrophage also indicated the decrease in the binding activity of both AGE and LPS.The function of these genes in vivo is different from those studied in vitro, and mouse developmental biological technics, especially gene targeting provide a nice tool to analyze these problems.
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