1993 Fiscal Year Final Research Report Summary
GENETIC STUDY OF A CHILDHOOD DISEASE AFFECTNG INTRACELLULAR CHOLESTEROL TRANSPORT
| Project/Area Number |
04670597
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | TOTTORI UNIVERSITY |
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Principal Investigator |
OHNO Kousaku Tottori University Faculty of medicine, Department of Neurobiology, Professor, 医学部, 教授 (70112109)
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| Co-Investigator(Kenkyū-buntansha) |
AKABOSHI Shinjiro Tottori University Hospital, Division of Child Neurology, Lecturer, 医学部・附属病院, 助手 (90231810)
NANBA Eiji Tottori University Hospital, Division of Child Neurology, Assitant Professor, 医学部・附属病院, 講師 (40237631)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Niemann-Pick Desease / cholesterol transport / selectable markers / gene cloning / immotalized cell |
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| Research Abstract |
Basic defectin type C Niemann-Pick disease is unknown. As an attempt to isolate the gene defectivein type C Niemann-Pick Disease, we have established an immortalized 3T3 cell line from sphingomelinosis mouse and found the cells show the same abnormalitis found in fibroblasts from patients with type C Niemann-Pick disease. In course of studies to characterizecholesterol metabolism in type C Niemann-Pick disease, we have fund fibroblasts from the patients have an increasedde novo pathway of cholesterol biosynthesis. When cells ara exposed to cholesterol biosynthetic inhibitors, they showed abnormal sensitivities. They showed marked hypersensitivity to cytotoxic effect of vitamin D3. The drug should be very useful to enrich and isolate a few cells restored cholesterol metabolism after transfecting human normal cDNA or genomic DNA.In addition, by transfer of a human chromosome into 3T3 cell line from sphingomyelinosis mouse, we have found a human chromosome 18 restore the cholesterol metabolism. BY Southern analysis, the gene locus is assigned to distal portion of the chromosome. These results suggest that the gene defective in type C Niemann-Pick disease could be isolated by expresstion cloning using the mouse cell line and the selectable drug or by positional cloning
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