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doi: 10.1242/10.1242/dev.00403

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HIF1 is a critical regulator of secretory differentiation and activation, but not vascular expansion, in the mouse mammary gland

¹ Division of Biological Sciences, Molecular Biology Section, University of California San Diego, La Jolla, CA 92093, USA
² Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
³ University of Colorado Health Science Center, Department of Physiology, Denver, CO 80262, USA
⁴ Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA
⁵ Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA

^* Author for correspondence (e-mail: rjohnson{at}biomail.ucsd.edu)

Accepted 15 January 2003

During pregnancy the mammary epithelium and its supporting vasculature rapidly expand to prepare for lactation, resulting in dramatic changes in the micro-environment. In order to investigate the role of oxygenation and metabolism in these processes, the oxygen-responsive component of the hypoxia-inducible factor (HIF) 1 complex, HIF1, was deleted in the murine mammary gland. Although vascular density was unchanged in the HIF1 null mammary gland, loss of HIF1 impaired mammary differentiation and lipid secretion, culminating in lactation failure and striking changes in milk composition. Transplantation experiments confirmed that these developmental defects were mammary epithelial cell autonomous. These data make clear that HIF1 plays a critical role in the differentiation and function of the mammary epithelium.

Key words: Hypoxia, HIF1, Mammary gland, Lactation, Differentiation, Metabolism, Mouse

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