The coordination of the hypoxic response is attributed, in part, to hypoxia-inducible factor 1α (Hif-1α), a regulator of hypoxia-induced transcription. After the teleost-specific genome duplication, most teleost fishes lost the duplicate copy of Hif-1α, except species in the cyprinid lineage that retained both paralogues of Hif-1α (Hif1aa and Hif1ab). Little is known about the contribution of Hif-1α, and specifically of each paralogue, to hypoxia tolerance. Here, we examined hypoxia tolerance in wild-type (Hif1aa+/+ab+/+) and Hif-1α knockout lines (Hif1aa-/-; Hif1ab-/-; Hif1aa-/-ab-/-) of zebrafish (Danio rerio). Critical O2 tension (Pcrit; the partial pressure of oxygen (PO2) at which O2 consumption can no longer be maintained) and time to loss of equilibrium (LOE), two indices of hypoxia tolerance, were assessed in larvae and adults. Knockout of both paralogues significantly increased Pcrit (decreased hypoxia tolerance) in larval fish. Prior exposure of larvae to hypoxia decreased Pcrit in wild-type fish, an effect mediated by the Hif1aa paralogue. In adults, individuals with a knockout of either paralogue exhibited significantly decreased time to LOE but no difference in Pcrit. Together, these results demonstrate that in zebrafish, tolerance to hypoxia and improved hypoxia tolerance after pre-exposure to hypoxia (pre-conditioning) are mediated, at least in part, by Hif-1α.
Keywords: critical oxygen tension; development; hypoxia tolerance; hypoxia-inducible factor; loss of equilibrium; zebrafish.