| Co-Investigator(Kenkyū-buntansha) |
YAMADA Hiroki TEIKYO UNIVERSITY,DEPARTMENT OF NEUROLOGY,RESEARCH FELLOW, 医学部, 助手 (90260926)
USUKI Fusako TEIKYO UNIVERSITY,DEPARTMENT OF NEUROLOGY,LECTURER, 医学部, 講師 (50185013)
MATSUMURA Kiichiro TEIKYO UNIVERSITY,DEPARTMENT OF NEUROLOGY,ASSOCIATE PROFESSOR, 医学部, 助教授 (50260922)
|
|---|
| Research Abstract |
The project started at 1993 to aim to develop a new therapy for Duchenne muscular dystrophy by study of regulatory mechanism of a dystrophin homologue, DRP or utrophin. The first goals were 1.analysis of total DRP gene structure, 2.development of a specific antiDRP antibody, and 3.determination of regulatory factors for DRP gene expression. At the beginning of the project, goal 1 was achieved by other investigators and the second goal 2 was done. The antiDRP spcific antibody and DRP message disclosed a wide expression of DRP protein or message in varied tissues including endothelial cells and nervous tissues. In addition, it was supprised that DRP was not only localized at plasm membrane but also in the cytoplasma. The data suggest that DRP may play a unclarified but important rloe (s) in a wide variety of cells. Regulatory factors for DRP gene expression could not be identified, although dibutyryl cAMP was found to be a specific upregulator for dystrophin. Physiological function of DRP is now essential for development of a therapy for DMD,because upregulation of DRP can play a unexpected function in nonmuscle cells.
For study of DRP in nonmuscle cells, we choosed Schwann cells because of the amount of DRP expression. In Schwann cells, DRP and dystrophin isoform, Dp116, was identified at both plasma membrane and cytoplasma by immunostainings. So-called dystrophin-associated (glyco) proteins (DAGs) were quite different in Schwann cell from muscle. 1.Dystroglycan complex were alpha dystroglycan, 120kD in stead of 156kD in muscle, and beta dystroglycan, 43kD,2.sarcoglycan complex was not present, 3.syntrophin complex was not identified. Dystroglycan complex was a dual receptor for nervous laminin and agrin dependent on Ca ions. Sialic acid was essential for binding between laminin/agrin and alpha dystroglycan. We are now going to analyze myelinogenesis in mutation of DRP/Dp116, dystroglycan complex and/or laminin/agrin.
|
