Elucidation of molecular architecture of neuromuscular junction and dissection of molecular pathomechanisms of congenital myasthenic syndromes

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04840
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: Ohno Kinji 名古屋大学, 医学系研究科, 教授 (80397455)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 先天性筋無力症候群 / アセチルコリン受容体 / Rspo2 / GFPT1 / iPS細胞

Outline of Final Research Achievements

Laser capture microdissection of the mouse spinal motor neurons (SMN) revealed that Rspo2 is highly expressed in spinal motor neurons. Rspo2 induces acetylcholine receptor (AChR) clustering, which is ~80% as potent as agrin. Tissue-specific rescue of Rspo2 by transgenic expression of Rspo2 by SMN- and muscle-specific promoters revealed that SMN-derived Rspo2 plays essential roles in the formation of the neuromuscular junction and AChR clustering. We propose that Rspo2 is an essential AChR clustering-inducing molecule after agrin.
We started dissection of molecular pathomechanisms of mutations in a gene encoding glycosylation enzyme, GFPT1, which were identified in Japanese patients with congenital myasthenic syndrome.

Free Research Field

神経遺伝情報学