Acute postnatal ablation of Hif-2alpha results in anemia.

Acute postnatal ablation of Hif-2alpha results in anemia. Research Abstract Details 

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Acute postnatal ablation of Hif-2alpha results in anemia. Abstract Text:

Michaela Gruber,Cheng-Jun Hu,Randall S Johnson,Eric J Brown,Brian Keith,M Celeste Simon,

Adaptive transcriptional responses to oxygen deprivation (hypoxia) are mediated by the hypoxia-inducible factors (HIFs), heterodimeric transcription factors composed of two basic helix-loop-helix-PAS family proteins. The transcriptional activity of HIF is determined by the hypoxic stabilization of the HIF-alpha proteins. HIF-1alpha and HIF-2alpha exhibit high sequence homology but have different mRNA expression patterns; HIF-1alpha is expressed ubiquitously whereas HIF-2alpha expression is more restricted to certain tissues, e.g., the endothelium, lung, brain, and neural crest derivatives. Germ-line deletion of either HIF subunit is embryonic lethal with unique features suggesting important roles for both HIF-alpha isoforms. Global deletion of Hif-2alpha results in distinct phenotypes depending on the mouse strain used for the mutation, clearly demonstrating an important role for HIF-2alpha in mouse development. The function of HIF-2alpha in adult life, however, remains incompletely understood. In this study, we describe the generation of a conditional murine Hif-2alpha allele and the effect of its acute postnatal ablation. Under very stringent conditions, we ablate Hif-2alpha after birth and compare the effect of acute global deletion of Hif-2alpha and Hif-1alpha. Our results demonstrate that HIF-2alpha plays a critical role in adult erythropoiesis, with acute deletion leading to anemia. Furthermore, although HIF-1alpha was first purified and cloned based on its affinity for the human erythropoietin (EPO) 3' enhancer hypoxia response element (HRE) and regulates Epo expression during mouse embryogenesis, HIF-2alpha is the critical alpha isoform regulating Epo under physiologic and stress conditions in adults.

Acute postnatal ablation of Hif-2alpha results in anemia. Publishing Authors By Initials

M Gruber,CJ Hu,RS Johnson,EJ Brown,B Keith,MC Simon,

For similar pathological conditions, signs and symptoms: pathologic processes: stress research abstracts see: pathological conditions, signs and symptoms: pathologic processes: stress research

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Acute postnatal ablation of Hif-2alpha results in anemia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 2301-6

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 6

MONTH: 02

YEAR: 2007

Acute postnatal ablation of Hif-2alpha results in anemia. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

Acute postnatal ablation of Hif-2alpha results in anemia. Keywords Mesh Terms:

KEYWORDS: Stress

MESH TERMS: genetics

Chemical & Substance for Abstract: Acute postnatal ablation of Hif-2alpha results in anemia. Information

Substance Name: Erythropoietin

Registry Number: 11096-26-7

Grant and Affiliation Information for Acute postnatal ablation of Hif-2alpha results in anemia.

AFFILIATION: Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Country: United States

AGENCY: United States PHS

GRANT: 66310

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MEDLINETA: Proc Natl Acad Sci U S A

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