A novel mechanism involving USP53-regulated BSEP trafficking underlies low-GGT intrahepatic cholestasis.

Background And Aims: USP53 variants cause low-GGT progressive familial intrahepatic cholestasis (PFIC). The mechanism is not well understood. USP53, which encodes a ubiquitin-specific protease, has been proposed to be involved in blood-bile barrier impairment.

A liver-specific mouse model for MYO5B-associated cholestasis reveals a toxic gain-of-function as underlying disease mechanism.

Myosin Vb (MYO5B) deficiency, referring to the loss of protein expression or function, causes microvillus inclusion disease (MVID) and/or progressive familial intrahepatic cholestasis-type 10 (PFIC10) in humans. MYO5B plays a role in intracellular trafficking, but the mechanisms by which it contributes to cholestasis are not understood. The aim of this study was to generate a liver-specific mouse model and investigate the mechanism of MYO5B-associated cholestasis.

Loss of hepatocyte Usp53 protects mice from a form of xenobiotic-induced liver injury.

Background: Ubiquitin-specific protease 53 (USP53) deficiency is associated with familial intrahepatic cholestasis in which serum gamma-glutamyl transferase (GGT) activity is relatively low. However, how USP53 deficiency contributes to cholestasis is obscure. No animal model has been reported.