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Netherton syndrome (NS) is caused by mutations in the SPINK5 gene. Several Spink5-deficient mouse models were generated to understand the mechanisms of NS  in vivo . However, Spink5-deficiency in mice is associated with postnatal lethality that hampers further analysis. Here we present a viable mouse model for NS generated by mosaic inactivation of the Spink5 gene. We propose that these mice are a valuable experimental tool to study NS, especially for long-term studies evaluating potential therapeutic compounds. Furthermore, we show that mosaic inactivation of a gene using TALENs or CRISPR/Cas9 systems can be used to study lethal phenotypes in adult mice.

A viable mouse model for Netherton syndrome based on mosaic inactivation of the Spink5 gene