| Project/Area Number |
17590871
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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 | Nagoya University |
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Principal Investigator |
KOIKE Haruki Nagoya University, Graduate School of Medicine, Medical Staff, 医学部附属病院, 医員 (80378174)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Masahiko Aichi Gakuin University, Faculty of Psychological and Physical Science, Professor, 心身科学部, 教授 (40378039)
SOBUE Gen Nagoya University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (20148315)
HATTORI Naoki University Hospital, Reseach Associate, 医学部附属病院, 助手 (10402570)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Charcot-Marie-Tooth disease / hereditary neuropathy / myelin protein zero / Schwann cell / mouse model |
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| Research Abstract |
Charcot-Marie-Tooth disease (CMT) is a hereditary disorder. Patients with this disorder generally manifest slowly progressive sensori-motor neuropathy with predominant involvement of distal portion of the lower extremities. It is divided into two categories (demyelinating and axonal forms) based on its electrophysiologic and histopathologic features. Patients with axonal form usually are characterized by relatively late-onset of disease and poor functional prognosis. On the other hand, recent studies have suggested that axonal damage and subsequent nerve fiber loss also are important for functional prognosis of the demyelinating form of patients. We used β-actin promotor and CNTF mini-promotor as vectors for induction because the timing and amount of the gene expression of mutant MPZ in Schwann cells is very important for establishment of mouse-model of axonal and demyelinating forms of MPZ-CMT. We aimed to establish mouse-lines with various amount of exogenous genes by inducing mutations in full size-wild type MPZ DNA clones derived form human peripheral nerves and making vectors for mutant genes causing axonal and demyelinating forms. On the other hand, we performed analyses of gene expression profile and DNA polymorphism in the peripheral nerve of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which is an acquired disease, using human DNA microarray chip. We also assessed clinical features of CIDP, electophysiologically and pathologically dividing into two subgroups of the axonal and demyelinating types. The results indicated that polymorphism of a gene encoding protein located around the node of Ranvier related to the axonal involvement of CIDP. We are interested in further studies concerning these issues because the molecule relating to axonal involvement and subsequent functional prognosis is deeply related to adhesion function, similar to MPZ.
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