Vhl Conditional Knockout mouse models

Vhl encodes the mouse ortholog of human VHL, the substrate recognition subunit of a cullin 2 RING E3 ubiquitin ligase that assembles with elongin B, elongin C, CUL2, and RBX1 and binds hydroxylated prolines in the oxygen-dependent degradation domains of HIF1A and HIF2A after prolyl hydroxylase modification, thereby coupling oxygen and 2-oxoglutarate availability to hypoxia inducible factor destruction. Biallelic inactivation, usually 3p25 deletion plus a truncating or missense hit, initiates clear cell renal carcinoma and drives von Hippel-Lindau disease with hemangioblastoma, pheochromocytoma, and pancreatic neuroendocrine tumors, with clear genotype specificity since type 2C alleles retain HIF regulation while losing other functions. Germline nulls die in midgestation from placental vasculogenesis failure, so conditional nulls with Pax8-cre or Ksp-cadherin-cre are standard, generally combined with Pbrm1, Bap1, or Setd2 deletion because Vhl loss alone rarely produces carcinoma in mouse kidney. Choose nulls for HIF2A dependence and belzutifan response, missense knockins for genotype-phenotype dissection.

Conditional deletion of Vhl limits the genetic change to the lineage you choose. That helps in oncology, immunology, and metabolic work where systemic loss would muddy the read. After you confirm Cre specificity, crossing to Vhl floxed stock yields usable cohorts.