1996 Fiscal Year Final Research Report Summary
Study of molecular pathogenesis and treatment in lysosomal strage disease
| Project/Area Number |
07457178
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
OKADA Shintaro OSAKA University Medical School, Professor, 医学部, 教授 (30028609)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIGAKI Toshinori Osaka University Medical School, Assistant Professor, 医学部, 助手 (20283749)
TSUKAMOTO Hiroko Osaka University Medical School, Assistant Professor, 医学部, 助手 (50263281)
TANIIKE Masako Osaka University Medical School, Assistant Professor, 医学部, 助手 (30263289)
INUI Koji Osaka University Medical School, Associate Professor, 医学部, 助教授 (90175208)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Krabbe Disease / twitcher mouse / mutation analysis / promoter analysis / retrovirus vector / gene therapy |
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| Research Abstract |
Krabbe disease or globoid cell leukodystrophy is an autosomal recessive disorder caused by a deficiency of galactocerebrosidase (GALC) activity. Most cases of the disease are infantile forms, but later onset forms are also reported. We recently cloned the human and the mouse GALC cDNA.Untill now, we have analyzed 18 patients of Krabbe disease including 5 American patients. In Japanese, 12 base deletion and 3 base insertion mutation in exon 7 was found in 9 alleles of infantile Krabbe disease. Luzi reported large deletion in the GALC gene (about 30kb) in Caucasian inrfantile patients. The frequency was reported about 26%. We found the same deletion in the fibroblasts from American patients. This mutation was not found in the Japanese patients. Other point mutation was individual. T2621 missense mutation was found in 3 alleles in the Japanese infantile patients. From these results, 12 base deletion and 3 base insertion mutation in exon 7 and large deletion were main mutation for infantile Krabbe disease in the Japanese and Caucasian patients, respectively. In adults or late onset patients, several missense mutation were reported. In twitcher mouse, a nonsense mutation was found at codon 339. Twitcher mouse is comparable to the late onset type inspite of nonsense mutation. This is probably due to the difference of a myelination.
Studies on a large number of patients in different ethnic groups will be necessary to examine the genotype and phenotype correlation.
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