A Novel Model System to Identify Cellular and Molecular Defects Underlying Rare Genetic Disorders

The study presents a novel in vitro model using NTERT keratinocytes with AEC-related TP63 mutations to investigate Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC), a disorder caused by mutations in the TP63 gene. This model overcomes limitations of iPSC-derived keratinocytes by allowing large-scale production of disease-relevant material. N-AEC keratinocytes exhibit defects similar to those in AEC patient skin, such as downregulation of cell adhesion proteins and pathological features like intra-epidermal cysts. This model is a valuable tool for understanding skin fragility in AEC and other genetic skin disorders, aiding in the development of new therapeutic strategies.