The VHL tumor suppressor in development and disease: functional studies in mice by conditional gene targeting

Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):564-74. doi: 10.1016/j.semcdb.2005.03.006. Epub 2005 Apr 26.


The von Hippel-Lindau tumor suppressor pVHL plays a critical role in the pathogenesis of familial and sporadic clear cell carcinomas of the kidney and hemangioblastomas of the retina and central nervous system. pVHL targets the oxygen sensitive alpha subunit of hypoxia-inducible factor (HIF) for proteasomal degradation, thus providing a direct link between tumorigenesis and molecular pathways critical for cellular adaptation to hypoxia. Cell type specific gene targeting of VHL in mice has demonstrated that proper pVHL mediated HIF proteolysis is fundamentally important for survival, proliferation and differentiation of many cell types and furthermore, that inactivation of pVHL may, unexpectedly, inhibit tumor growth under certain conditions. Mouse knock out studies have provided novel mechanistic insights into VHL associated tumorigenesis and established a central role for HIF in the development of the VHL phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / embryology
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Disease Models, Animal*
  • Fetal Development / genetics
  • Fetal Development / physiology*
  • Gene Targeting* / methods
  • Kidney Neoplasms / embryology
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Mice
  • Mice, Knockout
  • Von Hippel-Lindau Tumor Suppressor Protein / antagonists & inhibitors
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / physiology*


  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, mouse