1996 Fiscal Year Final Research Report Summary
The pathomechanism and treatment of fatty liver. -The studies of lysosomal acid lipase.
| Project/Area Number |
07557050
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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 | 試験 |
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| Research Field |
Neurology
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| Research Institution | Fukui Medical School |
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Principal Investigator |
KURIYAMA Masaru Fukui Medical School, Professor, 医学部, 教授 (80107870)
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| Co-Investigator(Kenkyū-buntansha) |
AZUMA Takeshi Fukui Medical School, Lecturer, 医学部附属病院, 講師 (60221040)
YOSHIDA Hiroki Kagoshima University, Dept.Medicine, Professor, 医学部, 教授 (90036476)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Wolman disease / Lysosome / Acid lipase / Gene therapy / Fatty liver / Bone marrow transplantation / 遺伝子治療 / 骨髄移植 |
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| Research Abstract |
Wolman's disease is a lysosomal strange disease with acid lipase (LAL) deficiency, which results in massive accumulation of cholesteryl esters and triglycerides in most tissues of the body, except for central nervous system. We previously reported a rat model of Wolman's disease (Wolman rat), and cloned rat LALcDNA and identified the mutation in the Wolman rat. In the liver of Wolman rat, the lipid droplets were accumulated in membrane-bounded organellae, susupected lysosomes, and were also foumd near rough endoplasmic reticulum or Golgi's apparatus, suggesting the impairment of biosynthesis or excreation of lipoproteines. Triglycerides were mainly accumulated in hepatic parenchymal cells and cholesteryl esters were mainly in Kupper's cells.
The rat LALcDNA was inserted to retroviral LXSN vector at cloning site. The LXSN (X=RLAL) vector was transfected to ecotropic psi-cre packaging cell by the method of the calcium phosphate coprecipitation. The recombinant retrovirus titer estimated by LXSN (X=RLAL) viral producer cell line clone, was unsuccessfully low (2x10^2cfu/ml). In the experiment of bone marrow transplantation, the bone marrow cells (2x10^7cells/0.2ml of PMRI) obtained form limbs of normal rat was transfused through tail vein of the affected rat at age of 30 days. The treated rat survived longer than the affected rats which usually died within 120 days after birth. The bone marrow transplantation provided gain of body weight and improvement of the accumulated lipids and acid lipase activity in the affected rat. Wolman's disease will be a suitable candidate for bone marrow transplantation and gene therapy.
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