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Cbl-3-deficient mice exhibit normal epithelial development

  1. Author:
    Griffiths, E. K.
    Sanchez, O.
    Mill, P.
    Krawczyk, C.
    Hojilla, C. V.
    Rubin, E.
    Nau, M. M.
    Khokha, R.
    Lipkowitz, S.
    Hui, C. C.
    Penninger, J. M.

  2. Author Address

    Austrian Acad Sci, Inst Mol Biotechnol, IMBA, Dr Bohr Gasse 7, A-1030 Vienna, Austria Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2C1, Canada Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada NCI, Regulat Protein Funct Lab, NIH, Ft Detrick, MD 21702 USA Penninger JM Austrian Acad Sci, Inst Mol Biotechnol, IMBA, Dr Bohr Gasse 7, A-1030 Vienna, Austria
    1. Year: 2003
  2. Journal: Molecular and Cellular Biology
    1. 23
    2. 21
    3. Pages: 7708-7718
  4. Type of Article: Article
  1. Abstract:

    Cbl family proteins are evolutionarily conserved ubiquitin ligases that negatively regulate signaling from tyrosine kinase-coupled receptors. The mammalian cbl family consists of c-Cbl, Cbl-b, and the recently cloned Cbl-3 (also known as Cbl- c). In this study, we describe the detailed expression pattern of murine Cbl-3 and report the generation and characterization of Cbl-3-deficient mice. Cbl-3 exhibits an expression pattern distinct from those of c-Cbl and Cbl-b, with high levels of Cbl-3 expression in epithelial cells of the gastrointestinal tract and epidermis, as well as the respiratory, urinary, and reproductive systems. Cbl-3 expression was not detected in nonepithelial cells, but within epithelial tissues, the levels of Cbl-3 expression varied from undetectable in the alveoli of the lungs to very strong in the cecum and colon. Despite this restricted expression pattern, Cbl-3-deficient mice were viable, healthy, and fertile and displayed no histological abnormalities up to 18 months of age. Proliferation of epithelial cells in the epidermises and gastrointestinal tracts was unaffected by the loss of Cbl-3. Moreover, Cbl-3 was not required for attenuation of epidermal growth factor-stimulated Erk activation in primary keratinocytes. Thus, Cbl-3 is dispensable for normal epithelial development and function.

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