Project/Area Number |
10470159
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Institute for Development Research, Aichi Human Service Center |
Principal Investigator |
OOHIRA Atsuhiko Institute for Development Research, Aichi Human Service Center, Dept. Perinatol., Dept. Head, 周生期学部, 部長 (20101074)
|
Co-Investigator(Kenkyū-buntansha) |
TOKITA Yoshihito Institute for Development Research, Aichi Human Service Center, Dept. Perinatol., Researcher, 周生期学部, 研究員 (50291175)
AONO Sachiko Institute for Development Research, Aichi Human Service Center, Dept. Perinatol., Senior Researcher, 周生期学部, 主任研究員 (20231780)
|
Project Period (FY) |
1998 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥11,600,000 (Direct Cost: ¥11,600,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥5,000,000 (Direct Cost: ¥5,000,000)
|
Keywords | Neuroglycan C / Proteoglycan / Chondroitin sulfate / Brain / Neuron / Axon / Dendrite / Phosphorylation / 神経細胞 / 樹状突起 / 軸索 / 発生工学 / site-directed mutagenesis / ノックアウトマウス / パートタイムプロテオグリカン / トランスジェニックマウス |
Research Abstract |
Neuroglycan C (NGC) is a transmembrane chondroitin sulfate proteoglycan whose expression is restricted to the central nervous system. The purpose of this research project is to clarify the functions of NGC in the brain development mainly by genetic engineering. The followings are the major findings obtained during the term of this project. 1. The human NGC gene (registered as CSPG5) comprised six exons, was approximately 19 kilo bases in size, and was assigned to human chromosome band 3p21.3 by FISH. 2. The mouse NGC gene consisting of six exons was approximately 17 kilo bases in size, and was assigned to mouse chromosome band 9F1. 3. Three splicing variants of NGC (NGC-I, -II, and -III) were expressed in the brain of the rat, mouse and human. 4. NGC-III, a minor variant which has a peptide insert consisting of 27 amino acid residues in the cytoplasmic domain of NGC-I (the major one), was localized to the axons of a subset of primary cultured neurons, whereas other NGC variants existed on the dendrites of most cultured neurons. 5. NGC was phosphorylated at serine residue(s) in its ectodomain not only in the cytoplasm but also at the cell surface of primary cultured fetal rat neocortical cells. 6. Site-directed mutagenesis revealed that NGC has a single chondroitin sulfate chain at Ser123 on the mouse NGC core protein. 7. Using a targeting vector constructed by the Cre-lox P system, homozygote mice were produced. The homozygote mice are being mated with Cre-transgenic mice to obtain null mutant mice of NGC. The phenotype of the mutant mice remained to be examined.
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