1996 Fiscal Year Final Research Report Summary
Study on lipid metabolism and atherogenesis with transgenic mouse models
| Project/Area Number |
07044254
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YOKODE Masayuki Graduate school of Medicine, Kyoto University, 医学研究科, 講師 (20252447)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Nobuyo University of North Carolina, 医学部, 助教授
RUBIN Edward M University of California at Berkeley, 医学部, 主任研究員
IEHARA Noriyuki Graduate school of Medicine, Kyoto University, 医学研究科, 助手 (20281727)
DOI Toshio Graduate school of Medicine, Kyoto University, 医学研究科, 講師 (60183498)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Hyperlipidemia / Atherosclerosis / apolipoprotein E / apo (a) / Knockout mouse / Transgeric Mouse |
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| Research Abstract |
In the current study, we investigated the molecular mechanism of atherogenesis by using molecular biology and mouse biology. [1] The low density lipoprotein receptor is known to play a key role in regulation of the levels of plasma cholesterol. Yokode, the head investigator of current study, has previously shown that the liver has a unique molecular system to transfer the LDL receptor. To examine further the molecular mechanism of this trafficking pathway, a new transgenic mice expressing a missorted LDL receptor molecule, which could be distinguished from the wild type receptor. We are now studying the pathway for the receptor in the hepatocyte of this mouse. [2] By collaboration with Drs.Maeda and Rubin, we studied molecular mechanism for accumulation of foam cells, a typical feature of early lesion of atheroscleosis in apoE knockout mice. By injection with the antagonizing rat monoclonal antibody against murine c-fms, the receptor for macrophage colony stimulating factor (M-CSF), we demonstrated that M-CSF/c-fms has an essential role in the development of atheroma in these mice. [3] We also obtained apo (a) transgenic mive to study the effect of apo (a) on atherogenesis and vascular remodeling. [4] In order to conduct these experiments, we presented our data in American Heart Association Meeting held in New Orleans in November, 1996, and discussed with the two investigators.
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