A pig model carrying heterozygous point mutation of NCSTN simulates familial acne inversa and reveals dysregulated cholesterol biosynthesis via the Notch-pAMPK-HMGCR pathway

Model of the Role of the NCSTN mutation in impaired skin barrier in acne inversa. Notch and AMPK signaling are required for cholesterol biosynthesis in the skin to form a competent barrier. The decreased activity of γ-secretase resulted from NCSTN mutation decrease NICD and Hes1 expression. In response, Hes1 fails to inhibit AMPK activation, thereby inhibiting cholesterol biosynthesis that results in impairment of the skin barrier.