Autosomal Ichthyosis With Hypotrichosis Syndrome Displays Low Matriptase Proteolytic Activity and Is Phenocopied in ST14 Hypomorphic Mice

The study linked autosomal recessive ichthyosis with hypotrichosis (ARIH) to a point mutation in the ST14 gene, resulting in reduced activity of the matriptase protease. Researchers demonstrated that the G827R mutation in humans led to decreased proteolytic activity, affecting substrates like prostasin. To explore this further, they created ST14 hypomorphic mice with significantly reduced matriptase mRNA levels, which exhibited symptoms similar to ARIH, including ichthyosis, hypotrichosis, and tooth defects. The findings suggested that the reduced activity of the matriptase-prostasin proteolytic cascade was the cause of ARIH, and the mouse model provided a valuable tool for studying matriptase's role in various biological processes.