Genetic mutation damages DNA and alters RNA splicing in familial amyotrophic lateral sclerosis
Familial amyotrophic lateral sclerosis (FALS) is a neurological disease that has been linked to mutations in several different genes, including the gene encoding the DNA/RNA binding protein FUS.
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.