Deletion of the von Hippel-Lindau gene causes sympathoadrenal cell death and impairs chemoreceptor-mediated adaptation to hypoxia.

ABSTRACT: Mutations of the von Hippel-Lindau (VHL) gene are associated with pheochromocytomas and paragangliomas, but the role of VHL in sympathoadrenal homeostasis is unknown. We generated mice lacking Vhl in catecholaminergic cells. They exhibited atrophy of the carotid body (CB), adrenal medulla, and sympathetic ganglia. Vhl-null animals had an increased number of adult CB stem cells, although the survival of newly generated neuron-like glomus cells was severely compromised. The effects of Vhl deficiency were neither prevented by pharmacological inhibition of prolyl hydroxylases or selective genetic down-regulation of prolyl hydroxylase-3, nor phenocopied by hypoxia inducible factor overexpression. Vhl-deficient animals appeared normal in normoxia but survived for only a few days in hypoxia, pres

SUBMITTER: Macias D 

PROVIDER: S-EPMC4287976 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature