Title: Abnormal sympathoadrenal development and systemic hypotension in PHD3(-/-) mice
Authors: Bishop, Tammie
Gallagher, Denis
Pascual, Alberto
Lygate, Craig A
de Bono, Joseph P
Nicholls, Lynn G
Ortega-Saenz, Patricia
Oster, Henrik
Wijeyekoon, Bhathiya
Sutherland, Andrew I
Grosfeld, Alexandra
Aragones, Julian
Schneider, Martin
Van Geyte, Katie
Teixeira, Dania
Diez-Juan, Antonio
Lopez-Barneo, Jose
Channon, Keith M
Maxwell, Patrick H
Pugh, Christopher W
Davies, Alun M
Carmeliet, Peter
Ratcliffe, Peter J # ×
Issue Date: May-2008
Publisher: Amer soc microbiology
Series Title: Molecular and cellular biology vol:28 issue:10 pages:3386-3400
Abstract: 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-2 but not HIF-1 alpha, supporting the nonredundant involvement of a PHD3-HIF-2 alpha 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 sympathoadrenal functions, such as blood pressure regulation.
ISSN: 0270-7306
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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