Neuronal migration : its mechanism in normal development and pathologic changes in cerebral dysgenesis.
| Project/Area Number |
10670753
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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 |
Pediatrics
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| Research Institution | Jichi Medical School |
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Principal Investigator |
MIZUGUCHI Masashi Jichi Medical School, Department of Pediatrics, Associate Professor, 医学部, 助教授 (20209753)
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| Co-Investigator(Kenkyū-buntansha) |
TAKASHIMA Sachio National Institute of Neuroscience, NCNP, Director General, 神経研究所, 所長(研究職) (70038743)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Lissencephaly / Subcortical laminar heterotopia / Fukuyama type congenital muscular dystrophy / Tuberous sclerosis / doublecortin / DCAMKL1 / hamartin / fukutin / LIS1 / Ekerラット / Zellweger症候群 / tuberin / telencephalin / 全前脳症 |
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| Research Abstract |
1) Doublecortin is a product of the DCX gene responsible for X-linked lissencephaly and subcortical laminar heterotopia syndrome. DCAMKL 1 (or KIAA0369) is a calcium calmodulin-dependent kinase with high homology to doublecortin. We produced specific antibodies against these proteins, and studied their expression immunochemically and immunohistochemically. The results indicated specific expression of these proteins in the normally developing nervous system during the fetal period. Intense immunoreactivity was localilzed in migrating neurons. In migration disorders, doublecortin expression was downregulated in brains with Zellweger syndrome and in subcortical laminar heterotopia, whereas in those with tuberous sclerosis some abnormal giant cells showed its overdue expression.
2) Fukuyama type congenital muscular dystrophy (FCMD) is caused by a mutaion in the fukutin gene. We produced antibodies against fukutin protein, and studied its expression immunochemically and immunohisto-chemically. In brains of normal fetuses, high expression was noted in the granular layer at the cerebral surface, whereas fukutin was decreased in those of FCMD fetuses.
3) Tuberous sclerosis (TS) is caused by a mutation in either of the two tumor suppressor genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively. In this study, we produced antibodies against hamartin, and studied its expression immunochemically and immunohisto- chemically. In the brain, kidney and heart of control patients, hamartin and tuberin co-localized. They showed simlutaneous loss in TS brain lesions, as well as in TS-associated renal and cardiac hamartomas. The brains of Eker rats, an animal model of TSC2, were studied pathologically. Two novel brain lesions, cortical tuber and anaplastic ganglioglioma, were found.
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Report
(4 results)
Research Products
(30 results)
