Sdr9c7-KO Mouse

Sdr9c7 encodes short-chain dehydrogenase/reductase family 9C member 7. It is crucial for skin barrier function as it catalyzes the dehydrogenation of lipoxygenase products esterified in CerEOS, an important precursor for the corneocyte lipid envelope (CLE) [1,2]. The CLE is vital for the integrity of the permeability barrier in the stratum corneum, and Sdr9c7 is involved in the covalent binding of ceramides to proteins on the outer surface of the cornified cell envelope, which is essential for skin barrier formation [1,2].

In a mouse Sdr9c7-KO model, there was a loss of covalent binding of epidermal ceramides to protein, indicating a structural fault in the barrier [2]. Quantitative liquid chromatography-mass spectometry (LC-MS) assays in Sdr9c7 -/- epidermis showed an almost complete loss of a specific species of ω-O-acylceramide esterified with linoleate-9,10-trans-epoxy-11E-13-ketone, while other acylceramides related to the lipoxygenase pathway were in higher abundance [2]. Recombinant SDR9C7 catalyzed the dehydrogenation reaction, but ichthyosis mutants were inactive [2].

In conclusion, Sdr9c7 is essential for skin barrier formation through its role in the covalent binding of ceramides to proteins. The Sdr9c7-KO mouse model has provided important insights into the pathogenesis of skin diseases related to defective skin barrier function, such as ichthyosis [2].

References:

1. Takeichi, Takuya. 2020. SDR9C7 plays an essential role in skin barrier function by dehydrogenating acylceramide for covalent attachment to proteins. In Journal of dermatological science, 98, 82-87. doi:10.1016/j.jdermsci.2020.03.005. https://pubmed.ncbi.nlm.nih.gov/32305239/

2. Takeichi, Takuya, Hirabayashi, Tetsuya, Miyasaka, Yuki, Brash, Alan R, Akiyama, Masashi. . SDR9C7 catalyzes critical dehydrogenation of acylceramides for skin barrier formation. In The Journal of clinical investigation, 130, 890-903. doi:10.1172/JCI130675. https://pubmed.ncbi.nlm.nih.gov/31671075/