It is unclear how FUS mutations promote FALS-associated symptoms.
In the issue of the Journal of Clinical Investigation, Eric Huang and colleagues of the University of California San Francisco developed a transgenic mouse model of FUS-associated FALS. FUS-R521C mice exhibited phenotypes similar to patients, such as neurological dysfunction and pronounced DNA damage.
The authors identified brain-derived neurotrophic factor (Bdnf) as a target of mutant FUS.
Treatment of FUS-R521C neurons with BNDF only partially restored dendrite function.
Evaluation of spinal cords from FUS-R521C revealed that there were multiple defects in the transcription and splicing of genes associated with dendrite growth and function.