Published April 1, 2021 - More info
Autosomal dominant mutations of the RNA/DNA binding protein FUS are linked to familial amyotrophic lateral sclerosis (FALS); however, it is not clear how FUS mutations cause neurodegeneration. Using transgenic mice expressing a common FALS-associated FUS mutation (FUS-R521C mice), we found that mutant FUS proteins formed a stable complex with WT FUS proteins and interfered with the normal interactions between FUS and histone deacetylase 1 (HDAC1). Consequently, FUS-R521C mice exhibited evidence of DNA damage as well as profound dendritic and synaptic phenotypes in brain and spinal cord. To provide insights into these defects, we screened neural genes for nucleotide oxidation and identified brain-derived neurotrophic factor (
Haiyan Qiu, Sebum Lee, Yulei Shang, Wen-Yuan Wang, Kin Fai Au, Sherry Kamiya, Sami J. Barmada, Steven Finkbeiner, Hansen Lui, Caitlin E. Carlton, Amy A. Tang, Michael C. Oldham, Hejia Wang, James Shorter, Anthony J. Filiano, Erik D. Roberson, Warren G. Tourtellotte, Bin Chen, Li-Huei Tsai, Eric J. Huang
Original citation: J Clin Invest. 2014;124(3):981–999. https://doi.org/10.1172/JCI72723
Citation for this addendum: J Clin Invest. 2021;131(7):e149564. https://doi.org/10.1172/JCI149564
The RNA-sequencing data for this study have been deposited in the NCBI’s Sequence Read Archive (SRA PRJNA706035).
See the related article at ALS-associated mutation FUS-R521C causes DNA damage and RNA splicing defects.