2004 Fiscal Year Final Research Report Summary
Causative gene mutation and molecular mechanism in spinooerebellar degeneration
| Project/Area Number |
14370202
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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 |
Neurology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
SASAKI Hidenao Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (80281806)
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| Co-Investigator(Kenkyū-buntansha) |
YABE Ichiro Hokkaido Univ., Grad School of Med., Instructor, 大学院・医学研究科, 助手 (60372273)
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| Project Period (FY) |
2002 – 2004
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| Keywords | spinocerebellar degeneration / molecular mechanism / spinocerebellar ataxia / neurodegenerative disorder |
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| Research Abstract |
Spinocerebellar degeneration (SCD) is a group of etiologically heterogeneous disorders. In Japan, 60% of SCD are sporadic, the rest consists of various hereditary disorders. We first mapped novel locus of spinocerebellar ataxia type 14 (SCA14) in dominant SCA. SCA14 is caused by mutation of protein kinase C gamma (PKCG). Various missense mutations are segregated in the coding exon 4 of PKCG, and mostly of them manifest cerebellar ataxia with some clinical variations. PKCG is selectively expressed in cerebellar Purkinje cells and molecular mechanism causing selective neuronal degeneration is not known. We analyzed PKCG mutations in other SCA families whose responsible mutations are unknown. However, additional families carrying mutations of PKCG were not identified in our cohort, implying that SCA14 is an infrequent disorder in Japan. PKCG is a member of inositol phospholipid signaling pathway within cell, and phospholipase Cβ4(PLCβ4) is another member of this cascade. Since knockout mice of PLCβ4 gene manifest cerebellar ataxia, we searched for possible mutations in human SCA. However, responsible mutations are not identified so far analyzed. Studies for transgenic model is necessary to examine neuropathology and possible alteration of various gene expression in SCA14. In addition, further studies are needed to identify responsible genes in hereditary SCA whose causative mutations are not known.
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Research Products
(34 results)
