Increased ratio of large myelin protein zero (L-MPZ) in myelin leads to Charcot-Marie-Tooth disease-like neuropathy

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16267
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46010:Neuroscience-general-related
• Research Institution: Shimane University
• Principal Investigator: Otani Yoshinori 島根大学, 学術研究院医学・看護学系, 助教 (30815973)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: L-MPZ / リードスルー / シャルコー・マリー・トゥース病 / myelin protein Zero

Outline of Final Research Achievements

L-MPZ is an isoform of myelin protein zero (P0), containing additional 63 amino acids at C-terminus by translational readthrough mechanism in various species including human. However, a role of this protein is still uncertain.
We generated a mouse line (L-MPZ mice) that synthesizes only L-MPZ by CRSPR-Cas9 system. L-MPZ mice caused neuropathy like Charcot-Marie-Tooth disease (CMT). L-MPZ was not compensated function of P0 protein. This indicated that the function of L-MPZ was different from the function of P0. Heterozygote mice those had increased L-MPZ and decreased P0 levels demonstrated various conditions from normal to neuropathy phenotypes. Thus, increased ratio of L-MPZ/P0 may cause CMT phenotype. Our study indicates a new possibility of CMT pathogenesis caused by alteration of the L-MPZ/P0 ratio.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究は翻訳リードスルー産物である L-MPZ の機能を明らかにしていくことで髄鞘でのL-MPZ の生理的意義の解明や高等生物における新しい翻訳制御機構解明への応用といった基礎研究から L-MPZ を用いた CMT 病の病態解明や治療法への応用といった臨床研究にも貢献できる.