Mutations in TJP2 cause progressive cholestatic liver disease.
Melissa SambrottaSandra StrautnieksEfterpi PapouliPeter RushtonBarnaby E ClarkDavid A ParryClare V LoganLucy J NewburyBinita M KamathSimon LingTassos GrammatikopoulosBart E WagnerJohn C MageeRonald J SokolGiorgina Mieli-Verganinull nullJoshua D SmithColin A JohnsonPatricia McCleanMichael A SimpsonA S KniselyLaura N BullRichard J ThompsonPublished in: Nature genetics (2014)
Elucidating genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Here we show that protein-truncating mutations in the tight junction protein 2 gene (TJP2) cause failure of protein localization and disruption of tight-junction structure, leading to severe cholestatic liver disease. These findings contrast with those in the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species.