2006 Fiscal Year Final Research Report Summary
Development of transgenic mouse model of axonal-form CMT with MPZ mutation and therapeutic approach to CMT
| 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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| 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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[Journal Article] Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP.2005
Author(s)
Iijima M, Yamamoto M, Hirayama M, Tanaka F, Katsuno M, Mori K, Koike H, Hattori N, Arimura K, Nakagawa M, Yoshikawa H, Hayasaka K, Onodera O, Baba M, Yasuda H, Saito T, Nakazato M, Nakashima K, Kira J, Kaji R, Oka N, Sobue G.
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Journal Title
Neurology 64
Pages: 1471-1475
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Age associated axonal features in HNPP with 17p11.2 deletion in Japan.2005
Author(s)
Koike H, Hirayama M, Yamamoto M, Ito H, Hattori N, Umehara F, Arimura K, Ikeda S, Ando Y, Nakazato M, Kaji R, Hayasaka K, Nakagawa M, Sakoda S, Matsumura K, Onodera 0, Baba M, Yasuda H, Saito T, Kira J, Nakashima K, Oka N, Sobue G.
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Journal Title
J Neurol Neurosurg Psychiatry 76
Pages: 1109-1114
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The wide spectrum of clinical manifestations in Sjogren's syndrome-associated neuropathy.2005
Author(s)
Mori K, Iijima M, Koike H, Hattori N, Tanaka F, Watanabe H, Katsuno M, Fujita A, Aiba I, Ogata A, Saito T, Asakura K, Yoshida M, Hirayama M, Sobue G.
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Journal Title
Brain 128
Pages: 2518-2534
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Neuronal intranuclear hyaline inclusion disease showing motor-sensory and autonomic neuropathy.2005
Author(s)
Sone J, Hishikawa N, Koike H, Hattori N, Hirayama M, Nagamatsu M, Yamamoto M, Tanaka F, Yoshida M, Hashizume Y, Imamura H, Yamada E, Sobue G.
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Journal Title
Neurology 65
Pages: 1538-1543
Description
「研究成果報告書概要(欧文)」より
