1995 Fiscal Year Final Research Report Summary
Development of transgenic mice expressing human complement modulator
| Project/Area Number |
06454718
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Laboratory animal science
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| Research Institution | Osaka University Research Institute for Micobial Diseases |
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Principal Investigator |
OKABE Masaru Research Institute for Microbial Diseases, Associate Professor, 微生物病研究所, 助教授 (30089875)
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| Co-Investigator(Kenkyū-buntansha) |
SEYA Tsukasa Osaka Research Center for Adult Disease, Chief research, 第六部, 室長
NISHIMUNE Yoshitake Research Institute for Microbial Diseases, Professor, 微生物病研究所, 教授 (80029793)
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| Project Period (FY) |
1994 – 1995
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| Keywords | complement / transgenic mouse / virus receptor / reproductive immunology |
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| Research Abstract |
Production of transgenic mice which express CD46
The construct to make transgenic mice were checked using CHO cells in vitro. The checked construct which is consisted with SV40 SR alpha promoter and CD46 were used in transgenic mouse experiment. However, all the transgenic mice produced by this construct did not express CD46 on their cell surface. On the course of finding the cause of this silent expression, it was found that when the cytosolic tail of CD46 were eliminated, the rest of the CD46 were expressed. Further experiment using transgenic mice also revealed that the origin of the silencer effect is derived form the nontranslated 3' region of the CD46 gene. By making the transgenic mice lacking CD46 3' untranslated region, we could produce the mice which express the CD46 on the cell surface.
Cloning of CD46 genomic gene.
The expression pattern of the above mentioned transgenic mice were limited to muscle, pancreas, lung and some more organs, and not strongly on the blood cells. The virus infection test was performed, but until now a very concrete evidence of the infection is not obtained. Therefore, to express CD46 as in the natural CD46 expressing cells, we cloned the genomic CD46 from human genomic library. At the present moment, we are now producing CD46 transgenic mice driven under CD46 promoter.
The role of CD46 in fertilization.
CD46 was shown to act in the complement regulation and also in sperm-egg fusion. In the seminal fluid, there are considerable amount of CD46. The CD46 in the seminal fluid was shown to exist on prostasome membrane and has an effect on complement regulation. The role of the prostasome CD46 was suggested to protecting sperm from complement attack in the vagina and uterus.
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