An activating mutation in the PDGF receptor alpha results in embryonic lethality caused by malformation of the vascular system

Authors

  • Patricia Kurth,

    1. Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany
    Current affiliation:
    1. University of Hohenheim, Institute of Genetics, Stuttgart, Germany
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  • Anne Moenning,

    1. Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany
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  • Richard Jäger,

    1. Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany
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  • Gaby Beine,

    1. Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany
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  • Hubert Schorle

    Corresponding author
    1. Department of Developmental Pathology, Institute of Pathology, University of Bonn Medical School, Bonn, Germany
    • Institute of Pathology, Department of Developmental Pathology, University of Bonn Medical School, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany
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Abstract

Platelet-derived growth factors (PDGF) and their receptors control cell proliferation, survival, and migration. To test the influence of an oncogenic mutation to embryonic development, a transgenic mouse line expressing PDGFRα (D842V) was established and analyzed. Most of the embryos die on embryonic day 12.5 due to massive hemorrhages in the trunk. In mesenchymal cells of mutant animals, proliferation is decreased while apoptosis is increased. Further analyses reveal that the aortic blood vessels are enlarged showing a reduced numbers of vascular smooth muscle cells (vSMC) around the aorta. We hypothesize that the process of aortic wall formation is impaired, leading to subsequent rupture and leakage of the blood vessel resulting in death of the embryos. We speculate that misexpression of PDGFRα in SMCs causes failure of vSMC recruitment to the aorta. Developmental Dynamics 238:1064–1072, 2009. © 2009 Wiley-Liss, Inc.

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