CRISPR/Cas9?mediated <i>grna</i> gene knockout leads to neurodevelopmental defects and motor behavior changes in zebrafish

Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions in early embryogenesis, anti-inflammation, and neurodegeneration. A good model for the functional study of PGRN zebrafish knockdown or knockout grn, gene encoding PGRN. Morpholino oligonucleotides (MOs) zinc finger nucleases have been used to generate grn models, yet they shown inconsistent phenotypes due either neurotoxicity MOs possible genetic compensation responses during editing. In this study, we generated stable grna (one major homologues zebrafish) by using CRISPR/Cas9-mediated genome sgRNA was designed target similar repeated sequence shared exon 13, 15, 19 zebrafish. The F1 generation frameshift mutation + 4 bp (the addition exon15), which causes premature termination, obtained subjected morphological behavioral evaluation. showed neurodevelopmental defects, including spinal motor neurons shorter axons, decreased sensory hair cells, thinning outer nuclear layer thickening inner retina, expression rhodopsin cone behavior changes. Moreover, could be rescued Tol2 system carrying gene. provides useful tool function has potential high-throughput drug screening disease therapy.