2000 Fiscal Year Final Research Report Summary
Generation of mouse models of human neurological disorders
| Project/Area Number |
10559009
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
広領域
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
SAKIMURA Kenji Brain Research Institute, Niigata University, Department of Cellular Neurobiology Professor, 脳研究所, 教授 (40162325)
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| Project Period (FY) |
1998 – 2000
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| Keywords | Cre-loxP recombination / conditional targeting / Neurological disorder model mouse / Glaucoma / Neuronal cell death / NMDA receptor channel |
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| Research Abstract |
The aim of this project is to develop model animals to elucidate the etiology and the disease mechanism of neurological disorders. For that purpose we carried out tow different studies. One is development of mouse models of neurological disorders using techniques of genetic and developmental engineering. The other is development of experimental models in which nerve cell degeneration is caused with the chronic process.
In the former study, we succeeded in developing a conditional targeting system using the P1 phage Cre/loxP recombination system. We have established a mouse line which can be used to mediate inducible gene recombination specifically in cerebellar Purkinje cells. In the generated mutant mice(D2CPR), the CrePR gene was specifically expressed in Purkinje cells under the control of the GluRδ2 gene promoter. When these mice were crossed with a reporter mouse line carrying the lacZ reporter gene under a universally active promoter, CrePR-mediated expression of β-galactosidase was induced specifically in mature Purkinje cells by the artificial progesterone receptor ligand UR486.
In the latter, we chose glaucoma as the nerve cell degeneration disease. In order to make a model of chronic ocular hypertension, a new method of measuring mouse optic pressure was developed. In addition, a method of raising mouse optic pressure for a long term was developed. Meanwhile, it was also clarified that the NMDA receptor channel took part in the degeneration of nerve cells caused by a transitory ischaemia.
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