Characterization of genetic loss-of-function of Fus in zebrafish

The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted <i>fus</i> in zebrafish (<i>Danio rerio</i>) using the CRISPR-Cas9 system. The <i>fus</i> knockout animals are fertile and did not show any distinctive phenotype. Mutation of <i>fus</i> induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3′UTR usage, which could mask the effects of loss of Fus. Unlike published <i>fus</i> morphants, maternal zygotic <i>fus</i> mutants do not show motoneuronal degeneration and exhibit normal locomotor activity.