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Endothelial apoptosis in Braf-deficient mice

Nature Genetics volume 16, pages 293–297 (1997)Cite this article

Abstract

Tyrosine kinase growth factor receptors and Ras/Raf/MEK/MAPK signalling have been implicated in the suppression1–3 as well as augmentation of programmed cell death4. In addition, a Ras-independent role for Raf as a suppressor of programmed cell death has been suggested by the recent finding that Craf1 interacts with members of the Bcl-2 family at mitochondrial membranes5. However, genetic studies of C elegans6 and Drosophila7, as well as the targeted mutagenesis of the murine Araf gene8, have failed to support such a role. Here we show that mice with a targeted disruption in the Braf gene die of vascular defects during mid-gestation. Braf−/− embryos, unlike Araf−/−8 or Craf1−/− embryos (L.W. et al., unpublished), show an increased number of endothelial precursor cells, dramatically enlarged blood vessels and apoptotic death of differentiated endothelial cells. These results establish Braf as a critical signalling factor in the formation of the vascular system and provide the first genetic evidence for an essential role of a Raf gene in the regulation of programmed cell death.

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Authors and Affiliations

  1. Section on Genetics, National Institute of Mental Health/National Human Genome Research Institute, Bethesda, Maryland, 20892, USA

    Leszek Wojnowski, Anne M. Zimmer, Heidi Hahn & Andreas Zimmer

  2. Intramural Research Support Program, SAIC-Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA

    Thomas W. Beck

  3. National Cancer Institute–Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA

    Ricardo Bernal

  4. Institute of Medical Radiation and Cell Research, University ofWürzburg, 97078, Wurzburg, Federal Republic of Germany

    Ulf R. Rapp

Authors
  1. Leszek Wojnowski
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Wojnowski, L., Zimmer, A., Beck, T. et al. Endothelial apoptosis in Braf-deficient mice. Nat Genet 16, 293–297 (1997). https://doi.org/10.1038/ng0797-293

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