Toward a development of the novel drug-screening system based on monitoring autophagy dynamics

2014 Fiscal Year Final Research Report

• Project/Area Number: 24650189
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokai University
• Principal Investigator: HADANO Shinji 東海大学, 医学部, 教授 (60281375)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 脳神経疾患 / 脳・神経 / トランスレーショナルリサーチ / 動物 / 神経科学

Outline of Final Research Achievements

The autophagy-endolysosomal system is an evolutionally conserved degradation system that is tightly linked to a wide variety of physiological processes. Dysfunction of this system is associated with many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). In this study, we sought to generate a novel analytical tool for the autophagy-endolysosomal system in vivo. First, we generated the expression construct encoding mKeimaRed_LC3B chimeric protein, and successfully detected the bimodal excitation spectrum of mKeimaRed_LC3B in HeLa cells under starved conditions. Then, we microinjected it into fertilized eggs from C57BL/6 mice, and transplanted them into the oviduct of pseudopregnant recipient mice. As a result, we have successfully established 2 lines of transgenic mouse expressing mKeima-Red_LC3B, particularly in heart, skeletal muscle and the central nervous system. These mice could become useful tools for development of the new drug-screening systems.

Free Research Field

神経解剖学・神経病理学