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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
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Kidney development and gene expression in the HIF2alpha knockout mouse.

Brooke M Steenhard1, Paul B Freeburg, Kathryn Isom

  • 1Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|March 8, 2007
PubMed
Summary

Hypoxia-inducible transcription factor-2 alpha (HIF2alpha) is widely expressed in developing kidneys but is not essential for kidney vascular development or function.

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Developmental Biology

Background:

  • Hypoxia-inducible transcription factor-2 (HIF2) regulates genes crucial for vascularization, including VEGF and VEGFR-2.
  • HIF2 is a heterodimer of HIF2alpha and HIF1beta subunits.

Purpose of the Study:

  • To investigate the expression patterns of HIF2alpha during kidney development and maturation.
  • To determine the role of HIF2alpha in renal vascular development and kidney organogenesis.

Main Methods:

  • Utilized HIF2alpha/LacZ transgenic mice to map HIF2alpha transcription.
  • Employed light and electron microscopy, Western blotting, and ex vivo kidney culture (metanephroi) under normoxic and hypoxic conditions.
  • Performed quantitative real-time PCR to assess HIF1alpha and HIF3alpha expression in HIF2alpha knockouts.

Main Results:

  • HIF2alpha/LacZ expression was observed in renal endothelial cells, mesangial cells, vascular smooth muscle cells, and some epithelial cells during kidney development.
  • HIF2alpha null embryos showed no defects in renal vascular development, nephrogenesis, or Flk-1 protein levels.
  • HIF2alpha null metanephroi exhibited normal VEGF mRNA induction under hypoxia, and knockouts displayed appropriate expression of endothelial and glomerular markers.
  • No compensatory upregulation of HIF1alpha or HIF3alpha was detected in HIF2alpha null kidneys.

Conclusions:

  • HIF2alpha is widely transcribed in the developing kidney, particularly in vascular and smooth muscle cells.
  • Despite its broad expression, HIF2alpha is not essential for normal kidney vascular development, organogenesis, or response to hypoxia.
  • These findings suggest a non-critical role for HIF2alpha in kidney development under normoxic and hypoxic conditions.