Cbl-3-deficient mice exhibit normal epithelial development.
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.
Griffiths
Emily K
EK
Department of Medical Biophysics, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada M5G 2C1.
Sanchez
Otto
O
Mill
Pleasantine
P
Krawczyk
Connie
C
Hojilla
Carlo V
CV
Rubin
Evelyn
E
Nau
Marion M
MM
Khokha
Rama
R
Lipkowitz
Stan
S
Hui
Chi-Chung
CC
Penninger
Josef M
JM
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D004848:Epithelium / Q000033:anatomy & histology / Q000254:growth & development*; D005786:Gene Expression Regulation; D018390:Gene Targeting; D006801:Humans; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D015682:Retroviridae Proteins, Oncogenic; D050721:Proto-Oncogene Proteins c-cbl; D020928:Mitogen-Activated Protein Kinases; C422087:Cblc protein, mouse