6.2.1. Rodents

In order to investigate the mechanisms involved in innate and acquired intrahepatic cholestasis, BSEP knockout animal models (mice and rat) have been established [89,90]. Recently, the CRISPR/cas9 technology has been employed to knock out the BSEP gene in adult mice [91,92]. In all models, expression of BSEP was strongly reduced, thus providing an alternative experimental model for studying intrahepatic cholestasis and putative therapeutic intervention in rodents. Interestingly, the mouse models do not show signs of severe cholestasis as seen in humans, because these mice produce a large amount of poly-hydroxylated bile acids, which are excreted renally [93]. Wang et al. used this model system to suggest that P-glycoprotein (ABCB1) can act as a compensatory bile salt transporter, which alleviates the severity of cholestasis in BSEP knockout mice [94].
