Knockout of zebrafish colony-stimulating factor 1 receptor by CRISPR/Cas9 affects metabolism and locomotion capacity

Colony-stimulating factor 1 receptor (CSF1R) is a tyrosine kinase receptor and a key regulator of proliferation, differentiation, migration, and colonization in macrophage lineage cells. CSF1R was found to be involved in the pathogenesis of immune disorders, hematopoietic diseases, tissue damage, tumor growth and metastasis, and so on. Hence, understanding the role of CSF1R is important. CSF1R is highly conserved among vertebrates. In zebrafish, it is encoded by the colony-stimulating factor 1 receptor a (csf1ra) gene. In this study, a csf1ra^-/- zebrafish mutant line was generated using clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. csf1ra^-/- larvae lacked the yellow cast on their heads and over their flanks, while adult mutants had poorly formed stripes. RNA-sequence analysis revealed that genes related to bile acid secretion, fat digestion and absorption, and pancreatic secretion were differentially expressed in csf1ra^-/- mutants, which led to fatty changes in the liver. In addition, genes related to locomotion were also significantly changed, with the more active movement observed in csf1ra^-/- larvae. Our study demonstrated that csf1ra participates in the metabolic process and behavior. This study provides new insights into csf1ra function during zebrafish development.