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

This study introduces a novel in vitro model using NTERT keratinocytes to explore cellular and molecular defects in AEC syndrome, caused by TP63 mutations. By creating N-AEC keratinocytes that replicate AEC patient skin abnormalities, the model highlights key features like reduced cell adhesion, linked to skin fragility. It allows for unlimited production of disease-relevant material, overcoming previous model limitations, and provides insights into AEC pathogenesis and potential treatments. Additionally, the model reveals reduced ZNF750 gene expression in AEC skin and can be adapted for other genetic skin disorders, potentially aiding in new therapeutic developments.