2006 Fiscal Year Final Research Report Summary
Research for the pathogenesis and therapy of oculopharyngeal muscular dystrophy - by using cell and animal models
| Project/Area Number |
16590835
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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 | Kumamoto University |
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Principal Investigator |
UYAMA Eiichiro Kumamoto University School of Medicine, Graduate Scholl of Medicine, Neurology Advanced Biomedical Sciences, Assistant Professor, 医学部附属病院, 講師 (90185075)
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| Project Period (FY) |
2004 – 2006
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| Keywords | OPMD / PABPN1 / polyalanine disease / OPMD cell model / OPMD model mouse / intranuclear inclusion / rimmed vacuoles / reduction of IN aggregation and cell death |
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| Research Abstract |
[Back ground] Oculopharyngeal muscular dystrophy (OPMD) is a late-onset polyalanine disorder characterized by progressive ptosis, dysphagia, and limb weakness. Intranuclear, inclusions and rimmed vacuoles are pathological hallmarks. It is caused by heterozygous expansion of a 10-alanine, stretch to 12-17 alanine residues in the N-terminus of the PABPN1. [Purpose] To elucidate its molecular pathogenesis" and to establish its therapy, we performed 1) microarray analyses using gene chip including, 36000 kinds of mRNA for the muscle samples from OPMD model mice A13 and control mice. 2) therapeutic trials to prevent intranuclear aggregation of PABPN1 and cell death using congo red and doxyclcline, which can reduce amyloid aggregation for cell model of OPMD.3) immunohistochemical studies using various antibodies for muscular glycoproteins for the purpose of clarification of rimmed vacuoles formation in OPMD and its related disorder, distal myopathy with rimmed vacuoles (DMRV). [Results] 1)We found various 120 genes that related OPMD with down gegulation. We have continued to further studies to identify OPMD-related genes. 2) Aggregate formation and cytotoxicity in cell models of OPMD were reduced by Congo red or doxycycline. 3) We found that Aracchis hypoganea agglutinin (PNA) lectin reacted strongly with sarcolemmal glycoproteins in the DMRV patients but not with those in conrol subjects including OPMD. We clarified that impaired sialyl 0-glycan formation in muscular glycoproteins, including α-dystroglycan, occurs in DMRV.
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[Journal Article] Effective repetitive dystrophin gene transfer into skeletal muscle of adult mdx mice using : a helper-dependent adenovirus, vector, expressing, the coxackievirus and adenovirus receptor (CAR) and dystrophin.2005
Author(s)
Uchida Y, Maeda Y, Kimura E, Yamashita S, Nishida Y, Arima T, Hirano T, Uyama E, Mita S, Uchino M.
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Journal Title
J Gene Med 7
Pages: 1010-1022
Description
「研究成果報告書概要(欧文)」より
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