Abnormal sympathoadrenal development and systemic hypotension in PHD3 -/- mice

Tammie Bishop, Denis Gallagher, Alberto Pascual, Craig A. Lygate, Joseph P. De Bono, Lynn G. Nicholls, Patricia Ortega-Saenz, Henrik Oster, Bhathiya Wijeyekoon, Andrew I. Sutherland, Alexandra Grosfeld, Julian Aragones, Martin Schneider, Katie Van Geyte, Dania Teixeira, Antonio Diez-Juan, Jose Lopez-Barneo, Keith M. Channon, Patrick H. Maxwell, Christopher W. PughAlun M. Davies, Peter Carmeliet, Peter J. Ratcliffe

135 Citations (Scopus)


Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis. To better understand this function in vivo, we have created PHD3-/- mice and analyzed the neuronal phenotype. Reduced apoptosis in superior cervical ganglion (SCG) neurons cultured from PHD3-/- mice is associated with an increase in the number of cells in the SCG, as well as in the adrenal medulla and carotid body. Genetic analysis by intercrossing PHD3-/- mice with HIF-1a+/- and HIF-2a+/- mice demonstrated an interaction with HIF-2α but not HIF-1α, supporting the nonredundant involvement of a PHD3-HIF-2α pathway in the regulation of sympathoadrenal development. Despite the increased number of cells, the sympathoadrenal system appeared hypofunctional in PHD3-/- mice, with reduced target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal responses, and systemic blood pressure. These observations suggest that the role of PHD3 in sympathoadrenal development extends beyond simple control of cell survival and organ mass, with functional PHD3 being required for proper anatomical and physiological integrity of the system. Perturbation of this interface between developmental and adaptive signaling by hypoxic, metabolic, or other stresses could have important effects on key sympathoad-renal functions, such as blood pressure regulation.

Original languageEnglish
JournalMolecular and Cellular Biology
Issue number10
Pages (from-to)3386-3400
Number of pages15
Publication statusPublished - 01.05.2008

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


Dive into the research topics of 'Abnormal sympathoadrenal development and systemic hypotension in PHD3 -/- mice'. Together they form a unique fingerprint.

Cite this