Zebrafish affects congenital hearing by regulating Rho-GTPase signaling.

INTRODUCTION

, the homolog of the human Usher 1B syndrome pathogenic gene, , plays an important role in stereociliary development and maintenance, therefore, is critical for hearing and balance. However, the molecular mechanisms that regulate hearing and balance still need to be studied.

METHODS

In this study, we generated two independent zebrafish knockout lines using CRISPR/Cas9 technology. To investigate the effects of on hearing, YO-PRO-1 staining and startle response assay were used. To gain insight into the specific molecular mechanisms by which affects hearing, transcriptome sequencing and bioinformatics analysis were employed.

RESULTS

Our study showed that hair cells of -/- zebrafish can not take up YO-PRO-1 fluorescent dye and are insensitive to acoustic stimulation in -/- zebrafish compared to wild type. Genes related to the Rho GTPase signaling pathway, such as arhgap33, dab2ip, and arghef40, are significantly down-regulated in -/- zebrafish embryos at 3 dpf. GTP and ATP compensation can partially rescue the hair cell defects in knockout zebrafish.

DISCUSSION

Our findings suggest that zebrafish affects congenital hearing by regulating Rho GTPase signaling, and loss of leads to abnormal Rho GTPase signaling and impairs hair cell function. , , arhgap33, dab2ip, arghef40 and -/- fonts in the abstract are italicized. -/- is a superscript format.