Autoinflammatory Keratinization Disease With Hepatitis and Autism Reveals Roles for JAK1 Kinase Hyperactivity in Autoinflammation.

ABSTRACT: Heterozygous mutations in JAK1 which result in JAK-STAT hyperactivity have been implicated in an autosomal dominant disorder that features multi-organ immune dysregulation. This study identifies another previously unreported heterozygous missense JAK1 mutation, H596D, in an individual with a unique autoinflammatory keratinization disease associated with early-onset liver dysfunction and autism. Using CRISPR-Cas9 gene targeting, we generated mice with an identical Jak1 knock-in missense mutation (Jak1^{H595D/+;I596I/+;Y597Y/+} mice) that recapitulated key aspects of the human phenotype. RNA sequencing of samples isolated from the Jak1^{H595D/+;I596I/+;Y597Y/+} mice revealed the upregulation of genes associated with the hyperactivation of ty

SUBMITTER: Takeichi T 

PROVIDER: S-EPMC8761858 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature