2002 Fiscal Year Final Research Report Summary
Production of norbin (a novel neurite-outgrowth factor) deficient mouse
| Project/Area Number |
12640670
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
動物生理・代謝
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| Research Institution | Saitama Medical School (2001-2002)
Tokyo Metropolitan Organization for Medical Research (2000) |
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Principal Investigator |
MARUYAMA Kei Saitama Medical School Faculty of Medicine Professor, 医学部, 教授 (30211577)
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| Project Period (FY) |
2000 – 2002
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| Keywords | norbin / long term potentiation / neurite / differentiation / peripheral nerve system / gene targeting |
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| Research Abstract |
Norbin is a novel gene, which is localized in central and peripheral neurons. Its expression is increased in rat hippocampus slices by the treatment of tetraethylammonium, which induces the facilitation of synaptic transmission as long term potentiation induced by tetanus stimulation. When norbin was overexpressed in Neuro2a cells, neural culture cell line, neurite outgrowth was observed. From these results it was suggested that norbin is related to neural plasticity. Norbin was reported by another group as neurochondrin. Secreted norbin was shown to promote hydroxyapatide resorptive activity of bone marrow cells. Norbin is secreted from COS cells overexpressing it. No signal peptide sequence is observed in that of norbin, and it was secreted as a whole molecule without any processing. The deletion of C-terminal of the middle portion of norbin reduced the secretion. This secretion was not inhibited by brefeldin A. The secretory mechanism is worth for the future study. We could not obtain the homologous recombinant ES cells to make a norbin-deficient mouse. The very low efficiency of the homologous recombination of the norbin gene might be because of the gene structure of norbin. The random insertion strategy performed by a German group produced a norbin deficient mouse by chance. However, the insertion was very near the C-terminal region and this C-terminal region deficient norbin was expressed as much as wild one. No structural or functional changes were observed in the mutant mice. It was concluded that this C-terminal portion of norbin had no significant physiological meanings. The completely deficient mice were necessary for the further study on the physiological function of norbin.
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