1997 Fiscal Year Final Research Report Summary
Studies on the pathophysiology and gene therapy for adrenoleukodystrophy using knock-out mice
| Project/Area Number |
08457191
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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 |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
YAMADA Takeshi Department of Neurology, Kyushu University, Associate Professor, 医学部, 助教授 (50230462)
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| Co-Investigator(Kenkyū-buntansha) |
NAGANO Sukehisa Department of Neurology, Kyushu University, Resident, 医学部, 医員
FURUYA Hirokazu Department of Neurology Kyushu University, Lecturer, 医学部, 講師 (60253415)
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| Project Period (FY) |
1996 – 1997
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| Keywords | adrenoleukodystrophy / ALD / ALDP / knockout mice / very long chain fatty acid / beta-oxidation / VLACS / peroxisome |
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| Research Abstract |
X-linked adrenoleukodystrophy (ALD) is caused by the mutation of ALD protein (ALDP) gene.Its principal biochemical abnormality is the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids, due to the impairment of beta-oxidatation in the peroxisome. We clarify its pathophysiology using the ALDP-deficient mice.
VLCFA beta-oxidation in the ALD fibroblasts was not corrected by overxpression of VLACS only but done by overxpression of both VLACS and ALDP.Western blot analysis revealed that the VLACS protein was present in each tissue from the ALDP-deficient mouse. Liver peroxisomes were purified by Nycodenz gradient centrifugation. The VLACS protein was detected only in the peroxisomal fraction from the control mouse, while it was detected in the cytosol fraction as well as the peroxisomal fraction from the ALDP-deficient mouse. These results indicated that ALDP is involved in the transport of VLACS into the peroxisome and that VLACS can not catalyze VLCFA beta-oxidation unless localized in the peroxisome.
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