Human keratin 8 variants predispose to acetaminophen toxicity

Background and Aims: Keratins 8 and 18 (K8/K18) are the intermediate filaments of digestive epithelia and display an important cytoprotective function. Accordingly, K8/K18 variants predispose humans to chronic liver disease development/progression and to acute acetaminophen toxicity. Given that K8 G62C and K8 R341H are the most common K8 variants in Caucasians, we studied their hitherto unknown molecular effects in the newly generated transgenic K8 R341H overexpressors as well as in the previously described K8 G62C mouse. Methods: Alterations in gene expression profile were quantified by microarray analysis. Ana…