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

Purpose: Colony-stimulating factor 1 receptor (CSF1R), a tyrosine kinase receptor, is a key regulator in the proliferation, differentiation, migration and colonization of macrophage lineage cells. Under pathological conditions, CSF1R was not only involved in the pathogenesis of immune disorders and hematopoietic diseases, but also closely related to tissue damage and tumor growth and metastasis. Therefore, comprehensive understanding of CSF1R function is of great significance. Methods: In this study, a csf1ra-/- zebrafish mutant line was generated using clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. Results:The csf1ra-/- larvae were lack of the yellow cast on the head and over the flank, while the adult mutants had poorly formed stripes. The RNA-sequence analysis revealed that genes related to bile acid secretion, fat digestion and absorption and pancreatic secretion were differentially expressed in csf1ra-/- mutants, leading to the fatty change in the liver. Besides, genes related to locomotion were also significantly changed with more active movement in csf1ra-/- larvae and adults. Conclusions: Overall, our data reveal that csf1ra participates the metabolic process and behavior. This study provides new insight into the functions of csf1ra gene during the development in zebrafish. Overall design: Embryo mRNA of 3 days post fertilization (dpf) wild type (WT) and csf1ra-/-zebrafish