2006 Fiscal Year Final Research Report Summary
Molecular pathological and biochemical study on pathogenesis caused by mitochondrial DNA abnormalities
| Project/Area Number |
16390309
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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 | National Institute of Neuroscience, National Center of Neurology and Psychiatry |
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Principal Investigator |
GOTO Yu-ichi National Institute of Neuroscience, Department of Mental Retardation and Birth Defect Research, Director, 神経研究所疾病研究第二部, 部長 (20225668)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Mitochondrial DNA / single deletion / KearnsYSayre syndrome / mitochondrial disaease / cybrids / cytochrome c oxidase / MELAS / germanium |
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| Research Abstract |
1) Resequence analysis of whole mitochondrial DNA
The investigator analyzed whole mitochondrial DNA sequence of more than 250 patients with mitochondrial diseases. We found 14674 mutation within the glutamate tRNA in the patients with benign COX deficiency, two adjacent mutations of 3243 within leucine tRNA, 9155 mutation within tyrosine tRNA in the patient with severe renal involvement, 14559 mutation in the patient with optic atrophy and dystonia. Many candidate mutations for disease were also found (617, 8296, 12129, 14729 mutations in tRNA genes and 3481, 5698, 6890, 7444, 8114, 9035, 9801 mutations in protein-coding regions).
2) Molecular biological and biochemical analyses using culture cells from the patients
Cybrids made by fusion of patient-derived cell cytoplasts with rho-zero cells were analyzed biochemically. 14674, 3244 and 9155 mutations were proved to be causes for diseases.
3) Point mutations in the leucine tRNA region and anticodon modification defect
Point mutations such as 3243 and 3271 mutation present in MELAS patients had anticodon modification defect, but other mutation present in non-MELAS patients did not show the defect. It suggests that this modification defect had some relationship with MELAS phenotype.
4) Germanium-induced marmoset model of mitochondrial disease
Marmosets supplemented with 0.5% germanium exhibited deafness clinically. Pathological evidence for mitochondrial abnormalities was confirmed in the tissue of Corti apparatus in the internal ear.
5) Clinical summary of 136 patients with single deletion of mitochondrial DNA
We summarized kinds and frequency of the deletion, clinical phenotype, onset ages and so on in the 136 patients with single deletions of mitochondrial DNA. The study revealed that the length of the deletion, COX subunit involvement in the deleted region, and early onset were risk factors for Kearn-Sayre syndrome.
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Research Products
(35 results)
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[Journal Article] Vascular involvement on a patient with mitochondrial mypathy, encephalopathy, lactic acidosis, and stroke-like episodes.2005
Author(s)
Takahashi N, Shimada T, Murakami Y, Katoh H, Oyake N, Ishibashi Y, Nishino I, Nonaka I, Goto Y
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Journal Title
The American Journal of Medical Sciences 329巻5号
Pages: 265-266
Description
「研究成果報告書概要(和文)」より
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[Journal Article] MIDAS/GPP34, a nuclear gene product, regulates total mitochondri al mass in response to mitochondrial dysfunction.2005
Author(s)
Nakashima-Kamimura N, Asoh T, Ishibashi Y, Mukai Y, shidara Y, Oda H, Munakata K, Goto Y, Ohta S
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Journal Title
Journal of Cell Science 118巻22号
Pages: 5357-5367
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Vascular involvement in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.2005
Author(s)
Takahashi N, Shimada T, Murakami Y, Katoh H, Oyake N, Ishibashi Y, Nishino I, Nonaka I, Goto Y
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Journal Title
Am J Med Sci 329(9)
Pages: 265-266
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction.2005
Author(s)
Nakashima-Kamimura N, Asoh S, Ishibashi Y, Mukai Y, Shidara Y, Oda H, Munakata K, Goto Y, Ohta S
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Journal Title
J Cell Sci 118(22)
Pages: 5357-5367
Description
「研究成果報告書概要(欧文)」より
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[Book] 今日の治療指針2005
Author(s)
後藤雄一(分担執筆)
Total Pages
1676
Publisher
医学書院
Description
「研究成果報告書概要(和文)」より
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[Book] 痴呆症学32004
Author(s)
後藤雄一(分担執筆)
Total Pages
391
Publisher
日本臨床
Description
「研究成果報告書概要(和文)」より
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[Book] 家庭医学百科2004
Author(s)
後藤雄一(分担執筆)
Total Pages
3229
Publisher
法研
Description
「研究成果報告書概要(和文)」より
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[Book] 今日の治療と看護2004
Author(s)
後藤雄一(分担執筆)
Total Pages
1586
Publisher
南江堂
Description
「研究成果報告書概要(和文)」より
