| Project/Area Number |
10557078
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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 | 展開研究 |
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| Research Field |
Pediatrics
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| Research Institution | JICHI MEDICAL SCHOOL |
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Principal Investigator |
MOMOI Mariko Jichi medical School, Department of Pediatrics, Professor, 医学部, 教授 (90166348)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Miki Jichi medical School, Department of Pediatrics, Instructor, 医学部, 助手 (20296114)
NOZAKI Yasuyuki Jichi medical School, Department of Pediatrics, instructor, 医学部, 助手 (90281295)
TSURU Tomohiko Jichi medical School, Department of Pediatrics, Assistant Professor, 医学部, 助手 (90296111)
斎藤 茂子 (斉藤 茂子) 自治医科大学, 医学部, 講師 (00260836)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | myotonic dystrophy / trinucleotide repeat disorder / hemiplegic migraine / spinocerebellar degeneration / late-onset cerebellar ataxia / caspase-8 / caspase-12 / 先天性筋ジストロフィー / 細胞死 / caspase-3 / 三塩基対リピート疾患 / 脆弱X症候群 / Pfu polymerase ポリメラーゼ / 毛根 / 遺伝子診断 / 筋強直性ジストロフィー / MT-PK遺伝子 / DMAHP遺伝子 |
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| Research Abstract |
Myotonic dystrophy is a neurodegenerative disorder in which abnormal extension of trinucleotide sequence is a causative gene abnormality, We have found a boy and mother who presented with myotonia, peripheral muscular atrophy, and mental retardation in the boy. DMPK analyses found that they did not carry the expanded trinucleotide repeat nor deletion or base substitutions. ZNF9 analyses showed that they did not have CCTG expansion in exon13. The presence of such cases suggested that multiple causative genes are involved in myotonic dystrophy. To investigate the olecular processes of neurodegeneration of trinucleotide disorders, the relation of polyQ aggregation and caspase-8 or caspase-12 activation was analyzed using antisera that specifically recognizes activated caspases. These studies suggested that polyQ aggregates induced caspase-12 activation and apoptosis via ER stress.
A family that presented with hemiplegic migrain and late-onset cerebellar ataxia was reported. A missense mutation in CACNA1A gene was detected. This suggested that CACN1A gene is causing a wide-variety of neurodegenerative diseases.
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