Loss of function of FUS/TLS in normal and pathological conditions

2016 Fiscal Year Final Research Report

• Project/Area Number: 25461299
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Meiji Pharmaceutical University (2014-2016); Institute of Physical and Chemical Research (2013)
• Principal Investigator: Kino Yoshihiro 明治薬科大学, 薬学部, 講師 (80415140)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: FUS/TLS / ALS / FTD / ノックアウトマウス / 神経変性疾患 / ポリグルタミン病 / RNA結合タンパク質 / ハンチントン病

Outline of Final Research Achievements

FUS/TLS is an RNA-binding protein associated with neurodegenerative diseases. Mutations of FUS/TLS are causative of amyotrophic lateral sclerosis (ALS), while FUS/TLS protein is accumulated in the inclusion bodies of a subset of frontotemporal lobar degeneration and polyglutamine diseases. However, pathological roles of FUS/TLS in these diseases have been elusive. We made homozygous FUS/TLS knockout mice, which showed some behavioral alterations but did not manifest ALS-like phenotypes. We then crossed TLS heterozygous mice with Huntington’s disease model mice and found that FUS/TLS heterozygosity worsened the HD phenotypes. In conclusion, our results indicate that loss of FUS/TLS function is not sufficient for causing ALS, while reduced function of FUS/TLS can modify the disease severity of HD.

Free Research Field

分子生物学