Constitutive gray hair in mice induced by melanocyte-specific deletion of c-Myc

Authors

  • Irina Pshenichnaya,

    1.  Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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  • Karine Schouwey,

    1.  Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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  • Marzia Armaro,

    1.  Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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  • Lionel Larue,

    1.  Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, France
    2.  CNRS UMR3347, Orsay, France
    3.  INSERM U1021, Orsay, France
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  • Paul S. Knoepfler,

    1.  Department of Cell Biology and Human Anatomy, University of California Davis School of Medicine, Sacramento, CA, USA
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  • Robert N. Eisenman,

    1.  Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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  • Andreas Trumpp,

    1.  German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Véronique Delmas,

    1.  Institut Curie, Centre de Recherche, Developmental Genetics of Melanocytes, Orsay, France
    2.  CNRS UMR3347, Orsay, France
    3.  INSERM U1021, Orsay, France
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  • Friedrich Beermann

    1.  Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
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Friedrich Beermann, e-mail: friedrich.beermann@epfl.ch

Summary

c-Myc is involved in the control of diverse cellular processes and implicated in the maintenance of different tissues including the neural crest. Here, we report that c-Myc is particularly important for pigment cell development and homeostasis. Targeting c-Myc specifically in the melanocyte lineage using the floxed allele of c-Myc and Tyr::Cre transgenic mice results in a congenital gray hair phenotype. The gray coat color is associated with a reduced number of functional melanocytes in the hair bulb and melanocyte stem cells in the hair bulge. Importantly, the gray phenotype does not progress with time, suggesting that maintenance of the melanocyte through the hair cycle does not involve c-Myc function. In embryos, at E13.5, c-Myc-deficient melanocyte precursors are affected in proliferation in concordance with a reduction in numbers, showing that c-Myc is required for the proper melanocyte development. Interestingly, melanocytes from c-Myc-deficient mice display elevated levels of the c-Myc paralog N-Myc. Double deletion of c-Myc and N-Myc results in nearly complete loss of the residual pigmentation, indicating that N-Myc is capable of compensating for c-Myc loss of function in melanocytes.

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