| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Yasuo Dept of Physiology, Keio Univ., School of Med.Instructor, 医学部, 助手 (60245462)
TACHI Nobutada School of Health Sciences, Sapporo Medical Univ.Associate Professor, 医学部, 講師 (80136944)
OHNISHI Akio Dept of Neurology, School of Med.University of Occupational & Environmental Heal, 医学部, 助教授 (50091278)
HAYASAKA Kiyoshi Dept of Padiatrics, Yamagata Univ.School of Med.Professor, 医学部, 教授 (20142961)
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| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1995: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1994: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Research Abstract |
Recentlygenetic studies on hereditary neuropathy progress remarkably. Genetic mutation of myelin proteins, such as P0, PASII/PMP22 and connexin 32 were reported in hereditary motor and sensory neuropathy (HMSN) type 1B,1A and XA,respectively. In this projects, we studied on peripheral myelin proteins and hereditary neuropathy from molecular and pathophysiological points of view. We demonstrated the characteristic localization of PASII/PMP22 and connexin 32 in compact myelin and Ranvier node of peripheral nerve, respectively. Functional analysis revealed promoting acitvity of neurite outgrowth in P0 protein and growtharrest activity of PASII/PMP22 protein, which may result in dysmyelination in case of overproduction of PASII/PMP22 such as HMSN type 1A.Among 80 cases of Japanese hereditary neuropathy, we found 65% of HMSN type 1A due to duplication and 10% hereditary neuropathy of liability to pressure palsies due to deletion of PASII/PMP22 gene, which were similar to those in Europe and United States. New point mutations were found such as G93R in PASII/PSP22, K131R,R96H in P0, and S26L,C53S in connexin 32 in HMSN type 1A,1B and XA,respectively. In the brother case of congenital hypomyelination neuropathy in HMSN type III,expression of P2 protein decreased characteristically, but no mutation was found in the reading frame of P2 gene. Relationship between these genetic mutations and disease phenotypes including histological changes and clinical symptoms was also studied. As related studies, we succeeded to visualize myelination process in vitro by oligodendrocyte using continuous video recording, which may useful to examine effective and/or inhibiting factors for myelination.
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