2005 Fiscal Year Final Research Report Summary
Studies on pathophysiology and experimental therapy of Ullrich's disease with collagen VI deficiency.
| Project/Area Number |
16590837
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Kagoshima University |
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Principal Investigator |
HIGUCHI Itsuro Kagoshima University, University Hospital, Faculty of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (80183573)
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| Co-Investigator(Kenkyū-buntansha) |
TAKASHIMA Hiroshi Kagoshima University, Graduate School of Medical and Dental Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (80372803)
OSAME Mitsuhiro Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (10041435)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Ullrich's disease / Bethlem myopathy / collagen VI / collagenopathy / laminin β1 / NG2 proteoglycan / experimental therapy |
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| Research Abstract |
Collagenopathies with collagen VI mutations include Ulirich congenital muscular dystrophy (Ullrich's disease) and Bethlem myopathy. Patients with Ullrich's disease have generalized muscle weakness, multiple contractures of the proximal joints and hyperextensibility of the distal joints. Bethlem myopathy is characterized by the combination of proximal muscle weakness and contractures of finger, elbow, and ankle joints. We found for the first time a deficiency of collagen VI in Ullrich's disease. Furthermore, we found an abnormality of cell adhesion and abnormal regeneration or maturation in Ullrich's disease. Mutations in the genes COL6A1, COL6A2, COL6A3 are associated with Ullrich's disease and Bethlem myopathy. Bethlem myopathy is inherited in an autosomal dominant manner and Ullrich's disease usually in an autosomal recessive manner. Recently, de novo dominant mutations are reported in Ullrich's disease. We evaluated the role of nonsense-mediated mRNA decay (NMD) in Ullrich's disease that has a frameshift mutation with a premature termination codon in the COL6A2 gene causing the loss of collagen VI. The pharmacological block of NMD caused upregulation of the mutant collagen VI and partially functional extracellular matrix formation. Our results suggest that NMD inhibitors can be used as a therapeutic tool to rescue some human genetic diseases exacerbated by NMD.
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Research Products
(4 results)
