Abstract IA013: A zebrafish model for VHL and hypoxia signaling

Abstract

Abstract he von Hippel-Lindau (VHL) tumor suppressor gene encodes an adaptor protein that regulates an array of transcription-dependent and -independent cellular and physiological processes. Mutations in this gene cause VHL disease, congenital polycythemia, renal cell carcinoma (RCC), and several other sporadic tumor types. Although different animal models for VHL disease have been adapted, the zebrafish VHL model offers distinct opportunities. Zebrafish vhl mutants develop key aspects of the human disease condition, including activation of the hypoxia-inducible factor (HIF) signaling pathway, polycythemia, excessive neovascularization, macular edema, and pronephric abnormalities resembling early stages of RCC. The zebrafish vhl model offers a platform for the identification of genetic pathways, modifiers, and interactors involved in the development of VHL-associated neoplasms. Vhl mutants represent a unique and clinically relevant in vivo model for studying genotype-phenotype correlations and the identification of prognostic biomarkers. The amenability of zebrafish for chemical genetic screens will not only be helpful to identify novel therapeutic agents but may also reveal novel processes that require regulation by VHL. Citation Format: Ellen van Rooijien, Stefan Schulte-Merker, Ive Logister, Emile Voest, Rachel Giles. A zebrafish model for VHL and hypoxia signaling [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr IA013.