Loss of one copy of vhl in zebrafish facilitates hypoxia tolerance

Abstract

Insufficient oxygen in the water (hypoxia) is one of the limiting factors for high-density culture in modern aquaculture. Hypoxia tolerance in fish has been reported to be related to the hypoxia-inducible factor (HIF)-α-mediated hypoxia signaling pathway. The well-defined function of the von Hippel-Lindau (VHL) tumor suppressor gene VHL is to mediate proteasomal degradation of hydroxylated HIF-α proteins, resulting in the downregulation of hypoxia signaling pathway. However, whether VHL has an impact on hypoxia tolerance is still elusive. In this study, we find that vhl+/- zebrafish have no gross defects in development, growth, reproduction, and movement. In addition, vhl+/- zebrafish also have normal vasculature. However, under hypoxia, vhl+/- zebrafish are more resistant to hypoxia treatment compared with their wildtype siblings. Further assays indicate that the number of erythrocytes is increased and the expression of hypoxia-responsive genes is enhanced in vhl+/- zebrafish compared with their wildtype siblings. These data indicate that loss of one copy of vhl in zebrafish facilitates hypoxia tolerance, revealing a function of vhl in hypoxia tolerance.