| Project/Area Number |
05454289
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
OKADA Shintaro Osaka University, Dept.Pediatr., Prof., 医学部, 教授 (30028609)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Hisao Osaka University, Dept.Pediatr., Assist.Prof., 医学部, 助手 (70199214)
INUI Koji Osaka University, Dept.Pediatr., Associate Prof., 医学部, 講師 (90175208)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1994: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1993: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | Krabbe disease / twitcher mouse / mutation analysis / gene therapy / galactosylceramidase / Krabbe病 / galactocerebrosidase / クローニング / twit cher mouse |
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| Research Abstract |
Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder that affects both the central and the peripheral nervous system due to the enzymatic defect of galactocerebrosidase. Recently, we have succeeded in cloning the cDNA.In this study molecular defects in Krabbe disease were investigated in twelve patients (seven Japanese and five non-Japanese patients) using cultured skin fibroblasts. We found six types of point mutations and 3 types of deletions. The low enzymatic activity of the cDNAs with the three mutations, nonsense mutation at codon 369 in a non Japanese typical infantile patient, two misssense mutation (Pro at codon 302 to Ala, Val at codon 550 to Gly) in a japanese late infantile patient and non-Japanese patient, were confirmed in expression studies. The P302A mutation was heterozygous and the V550G was homozygous in genomic analysis. A twelve base deletion with 3 base insertion was found in three infantile Japanese patients and not found in 30 controls. The mutation was homozygous in two patients and heterozygous in a patient, resulting in the 36% allele frequency in Japanese patients. In this study we for the first time clarified the molecular defects in krabbe disease.
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