The Roles of Smad2 and Smad3 in Mouse Skin Development

    June 2008 in “ The Knowledge Bank (The Ohio State University) ”
    Dina Bobrova
    TLDR Smad2 and Smad3 are essential for normal skin development, and their absence causes severe skin issues and cancer.
    The study investigated the roles of Smad2 and Smad3 in mouse skin development and tumorigenesis by deleting these proteins in murine skin to assess their impact on TGF-β signaling. Smad2 epithelial null/Smad3 null mutant mice exhibited severe skin abnormalities, hair loss, and early death, with more pronounced phenotypes than Smad4 mutants, including hyperkeratinosis and abnormal hair follicle positioning. Smad3 heterozygous mice with Smad2 knocked out in fibroblasts developed skin and oral cancerous lesions as adults, similar to Smad4 mutants. Histological analyses revealed increased apoptosis, cell proliferation abnormalities, and decreased collagen fibers in mutants. RT-PCR showed up-regulation of TGF-β target genes in tumors, indicating that defects in TGF-β signaling contributed to the observed skin and tumor phenotypes.
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