HIF1A Regulates Rhbg Expression to Enhance Ammonia Excretion in Amur Ide (Leuciscus waleckii) Under Extreme Alkaline Conditions

High-alkalinity water bodies can disrupt normal ammonia metabolism in fish, leading to ammonia poisoning. In China, there exists a highly tolerant group of Amur ide (<i>Leuciscus waleckii</i>) that can survive in extreme alkaline lakes with alkalinity up to 53.57 mM (pH 9.6), making it an excellent model for elucidating the high-alkalinity tolerance mechanism in fish. We have discovered that this species has evolved a special ammonia excretion mechanism to maintain ammonia efflux in high-alkalinity environments. Compared to the freshwater forms of Amur ide, the ammonia excretion protein RHBG plays a prominent role in the ammonia excretion process of the alkali forms of Amur ide; however, the regulatory mechanism of RHBG expression in fish remains unclear. Through DNA pull-down, RNA-Seq, qPCR, Western blotting, immunofluorescence, and dual-luciferase reporter assays, this study demonstrates that the transcription factor HIF1A can inversely regulate the expression of <i>Rhbg</i> by binding to its promoter region, thereby participating in the high-alkalinity adaptation process of fish. The findings of this study provide a theoretical basis for elucidating the ammonia excretion mechanism and revealing the alkalinity tolerance mechanism in fish.