2000 Fiscal Year Final Research Report Summary
GENE MAPPING OF MOYAMOYA DISEASE
| Project/Area Number |
11671358
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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 |
Cerebral neurosurgery
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| Research Institution | TOKYO MEDICAL & DENTAL UNIVERSITY, SCHOOL OF MEDICINE |
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Principal Investigator |
MATSUSHIMA Yoshiharu TOKYO MEDICAL & DENTAL UNIVERSITY, GRADUATE SCHOOL, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (20134679)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kiyotaka TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY, CHIEF RESEARCHER, 細胞生物部門, 主任研究員 (90073022)
AOYAGI Masaru TOKYO MEDICAL & DENTAL UNIVERSITY, SCHOOL OF MEDICINE, LECTURER, 医学部・附属病院, 講師 (40134704)
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| Project Period (FY) |
1999 – 2000
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| Keywords | moyamoya disease / linkage analysis / gene mapping |
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| Research Abstract |
We examined 8 moyamoya families. MRI angiography was routinely performed to examine whether each pedigree suffers from this disease. The familial moyamoya patients are seemed to inherit by a dominant manner. However, we suspect many nonpenetrant carriers may confuse the actual dominant inheritance. We examine the largest moyamoya families in which 7 moyamoya patients appeared. Taking genomic DNA from peripheral leukocytes, we tried to map the responsible gene for this familial moyamoya disease. We mostly use a candidate gene approach and occasionally random mapping. We identified a potential locus for these families and narrowed down the locus. The lod score for this locus is now 3.8, the value of which is statistically significant, and spanned within 19 cM.We then made the immortalized lymphoblast cell lines from affected and unaffected subjects of moyamoya families, took mRNA, and investigated the mutation for 6 candidate genes by SSCP or direct sequencing. We have not yet identified the responsible mutation for these genes. We further begun to randomly screen the expression of more then 10,000 genes by DNA tip technique. We examined the migratory and proliferative responses of cultured smooth muscle cells(SMC)between moyamoya and control subjects. The response to IL-1 was significantly different between them. IL-1 inhibited the migratory response of moyamoya SMC while it stimulated that of control SMC.This was explained by the up-regulation of COX-2 by IL-1 in moyamoya SMC, leading to overproduction of PGE2, resulting an increase in permeability of moyamoya vessels.
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