FUS IS ESSENTIAL FOR SOMATIC GROWTH AND SEXUAL SIZE DIMORPHISM IN ZEBRAFISH

The Fused in sarcoma gene (FUS) is a RNA-binding protein implicated in the regulation of transcription and pre-mRNA splicing. Mutations in FUS lead to neurodegenerative diseases including ALS (amyotrophic lateral sclerosis) in mammals. However, little is known about fus function in fish species. Here, we generated frame-shift alleles in the zebrafish fus gene using CRISPR/Cas9 mutagenesis. Homozygous fus^-/- zebrafish developed normally and were fully fertile, except that their body size and body weight were smaller than that of wild-type zebrafish at both the larvae and adult stages. In addition, the female-biased sexual size dimorphism in adult zebrafish was also eliminated when fus was mutated. The expression levels of several growth-related genes including gh1, ghra, igf1, igf2a, stat5.1 and socs6 were significantly reduced in fus^-/- zebrafish larvae compared with the wild-type. However, there was no effect on locomotor activity in fus^-/- zebrafish. Therefore, different from its functions in mammals, fus is not associated with motoneuron development and has a divergent function in regulating somatic growth and sexual size dimorphism in fish species.