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

Huiling Meng; Yue Shang; Yajia Cheng; Kexin Wang; Jing Yu; Peipei Cao; Saijun Fan; Yuhao Li; Jianlin Cui

doi:10.1016/j.bbrc.2021.02.122

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

Biochem Biophys Res Commun. 2021 Apr 30:551:93-99. doi: 10.1016/j.bbrc.2021.02.122. Epub 2021 Mar 13.

Authors

Huiling Meng¹, Yue Shang², Yajia Cheng¹, Kexin Wang¹, Jing Yu¹, Peipei Cao¹, Saijun Fan², Yuhao Li³, Jianlin Cui⁴

Affiliations

¹ Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Department of Pathology, Nankai University School of Medicine, Tianjin, 300071, China.
² Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.
³ Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Department of Pathology, Nankai University School of Medicine, Tianjin, 300071, China. Electronic address: liyuhao@nankai.edu.cn.
⁴ Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Department of Pathology, Nankai University School of Medicine, Tianjin, 300071, China. Electronic address: cuijianlin@nankai.edu.cn.

PMID: 33725575
DOI: 10.1016/j.bbrc.2021.02.122

Abstract

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.

Keywords: CRISPR/Cas9; Colony-stimulating factor 1 receptor a (csf1ra); Knock out; Locomotion capacity; Metabolism; Zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CRISPR-Cas Systems / genetics*
Gene Knockout Techniques
Larva / genetics
Larva / metabolism
Locomotion / genetics*
Mutation
Receptor, Macrophage Colony-Stimulating Factor / deficiency*
Receptor, Macrophage Colony-Stimulating Factor / genetics
Zebrafish / genetics*
Zebrafish / metabolism*

Substances

Receptor, Macrophage Colony-Stimulating Factor