Research Projects

2004 - 2005

Analysis of myasthenic disease caused by MuSK dysfunction

Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

Grant number
16590831
Japan Grant Number (JGN)
JP16590831
Grant amount
(Total)
3,600,000 Japanese Yen
(Direct funding)
3,600,000 Japanese Yen

Muscle-specific kinase (MuSK) is critical for the synaptic clustering of nicotinic acetylcholine receptors (AChR) and plays multiple roles in the organization and maintenance of neuromuscular junctions (NMJ). MuSK is activated by agrin, which is released from motoneurons, and induces AChR clustering at the postsynaptic membrane. Although autoantibodies against the ectodomain of MuSK have been found in a proportion of patients with generalized myasthenia gravis (MG), it is unclear whether MuSK autoantibodies are the causative agent of generalized MG. In the present study, rabbits immunized with MuSK ectodomain protein manifested MG-like muscle weakness with a reduction of AChR clustering at the NMJ. The autoantibodies activated MuSK and blocked AChR clustering induced by agrin or by mediators that do not activate MuSK. Thus, MuSK autoantibodies rigorously inhibit AChR clustering mediated by multiple pathways, an outcome that broadens our general comprehension of the pathogenesis of MG.

Link information
KAKEN
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16590831
ID information
  • Grant number : 16590831
  • Japan Grant Number (JGN) : JP16590831