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

Opened Access Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice
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Autor: Bishop, Tammie
Gallagher, Denis
Pascual Bravo, Alberto
Lygate, Craig A.
Bono, Joseph P. de
Nicholls, Lynn G.
Ortega Sáenz, Patricia
Oster, Henrik
Wijeyekoon, Bhathiya
Sutherland, Andrew I.
Grosfeld, Alexandra
Aragones, Julian
Schneider, Martin
Geyte, Katie van
Teixeira, Dania
Diez Juan, Antonio
López Barneo, José
Channon, Keith M.
Maxwell, Patrick H.
Pugh, Christopher W.
Davies, Alun M.
Carmeliet, Peter
Ratcliffe, Peter J.
Departamento: Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica
Fecha: 2008
Publicado en: Molecular and Cellular Biology, 28 (10), 3386-400.
Tipo de documento: Artículo
Resumen: 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_, supporting the nonredundant involvement of a PHD3–HIF-2_ 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...
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URI: http://hdl.handle.net/11441/17802

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