Severe Skin Permeability Barrier Dysfunction in Knockout Mice Deficient in a Fatty Acid Omega-Hydroxylase Crucial to Acylceramide Production

    July 2019 in “ Journal of Investigative Dermatology ”
    Masatoshi Miyamoto, Narumi Itoh, Megumi Sawai, Takayuki Sassa, Akio Kihara
    TLDR Lack of a key enzyme causes severe skin issues and death in mice.
    The study investigated the role of the fatty acid ω-hydroxylase enzyme Cyp4f39 in mice, analogous to human CYP4F22, in acylceramide production, crucial for skin barrier formation. Knockout mice lacking Cyp4f39 exhibited severe skin barrier dysfunction, leading to death within 8 hours of birth, due to increased transepidermal water loss and compromised skin integrity. Histological analysis showed impaired lipid lamella formation and structural abnormalities in the epidermis, with a near-complete loss of acylceramide and its precursor. These findings provided insights into the molecular mechanisms underlying skin barrier abnormalities and the pathogenesis of ichthyosis related to Cyp4f39 and CYP4F22 deficiencies, highlighting the enzyme's essential role in skin health and potential therapeutic strategies for related disorders.
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