CLDN1 and neonatal ichthyosis-sclerosing cholangitis syndrome: Furthermore, there are differences in the phenotype of TJ protein loss of function in mice and humans: e.g., while CLDN1 KO in a mouse model has shown to be lethal [52], congenital CLDN1 KO loss-of function mutations in human patients can manifest in a highly variable phenotype ranging normal health without disease to neonatal sclerosing cholangitis and ichthyosis of variable severity (NISCH syndrome), potentially due to compensatory upregulation of other CLDN members [56].