1997 Fiscal Year Final Research Report Summary
Studies on neural calcium signaling using knock-out mice
| Project/Area Number |
08458257
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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 | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Okazaki National Research Institutes |
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Principal Investigator |
IMOTO Keiji Okazaki National Research Institutes National Institute for Physiological Sciences, Professor, 生理学研究所, 教授 (00176512)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Calcium signaling / Calcium channel / Knock-out mouse / Ataxic mutant mouse |
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| Research Abstract |
We planned to introduce targetted disruption of the genes of P/Q type and N type voltage-gated calcium channels, but we failed to attain the goal. For producing calcium channel-knock-out mice, we had difficulties not only in establishing homologously recombinated ES cell lines but also in making chimeric mice by injecting the ES cells. It is not known why we had so many difficulties. But if we consider the current situation that no one has succeeded in knocking out calcium channel genes, there may be some specific regulatory mechanism for those genes.
In meantime, we continued to characterize functional properties in ion conduction and activation of calcium channels. Also we made molecular cloning of cDNAs encoding a new entity of calcium channels that are not voltage-dependent but activated by cell surface receptors through unidentified intracellular messengers. We obtained several cDNAs, and we are now characterizing their functional properties using a recombinant expresion system. A project to knock out one of this channel family is in progress. We have already established homologously recombinated ES cell lines, and expect to have chimeric mice in near future.
Because mutations in the P/Q type calcium channel gene can cause cerebellar ataxia and other neurological symptoms in mice and human, we studied cerebellar Purkinje cells electrophysiologically, and compared the functional properties with those we obtained in recombinant system. These results will give us an insight into the pathological mechanism of calcium channel defects.
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[Publications] Nakashima, Y., Nishimura, S., Maeda, A., Barsoumian, E.L., Hakamata, Y., Nakai, J., Allen, P.D., Imoto, K.and Kita, T.: "Molecular cloning and characterization of a human brain ryanodine receptor." FEBS Lett.417. 157-162 (1997)
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[Publications] Wakamori, M., Strobeck, M., Niidome, T., Teramoto, T., Imoto, K.and Mori, Y.: "Functional characterization of ion permeation pathway in the N-type Ca^<2+> channel." J.Neurophysiol.79. 622-634 (1998)
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[Publications] Mori, Y., Takada, Y., Okada, T., Wakamori, M., Imoto, K., Wanifuchi, H., Oka, H., Oba, A., Ikenaka, K.and Kurosaki, K.: "Differential distribution of TRP Ca^<2+> channel isoforms in mouse brain." Neuro Report. 9. 507-515 (1998)
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「研究成果報告書概要(欧文)」より
