Cbl-3-deficient mice exhibit normal epithelial development

Emily K Griffiths, Otto Sanchez, Pleasantine Mill, Connie Krawczyk, Carlo V Hojilla, Evelyn Rubin, Marion M Nau, Rama Khokha, Stan Lipkowitz, Chi-Chung Hui, Josef M Penninger

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)7708-18
Number of pages11
JournalMolecular and Cellular Biology
Volume23
Issue number21
Publication statusPublished - Nov 2003

Keywords

  • Animals
  • Cells, Cultured
  • Enzyme Activation
  • Epithelial Cells
  • Epithelium
  • Gene Expression Regulation
  • Gene Targeting
  • Humans
  • In Situ Hybridization
  • Keratinocytes
  • Mice
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases
  • Proto-Oncogene Proteins c-cbl
  • Retroviridae Proteins, Oncogenic
  • Tissue Distribution

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