The whole-body Fxr knockout (KO) mice (Fxr WB KO) were reported and are on a pure C57BL/6J genetic background.16 (link), 17 (link) The generation of tissue-specific Fxr KO mice on a mixed genetic background has been described previously using the loxP/Cre technology with specific disruption of the Nr1h4 gene in hepatocytes (Fxr Liv KO) or in enterocytes (Fxr Int KO).18 (link) Specifically, the Fxr Liv KO and Fxr Int KO mice were generated by crossbreeding Fxr floxed/floxed mice with albumin cre (+) or villin cre (+) mice. But these mice were on a mixed genetic background with variable basal expression of bile acid synthetic genes. So in the current study, the congenic Fxr Liv KO and Fxr Int KO mice in the C57BL/6J genetic background were produced. Shp KO mice and hepatocyte-specific Shp transgenic mice (Albumin promoter derived, Shp Tg) have been reported.19 (link), 20 (link) Fxr WB KO mice with hepatocyte-specific Shp over-expression (Fxr WB KO/Shp Tg) were generated via crossing Fxr WB KO mice with Shp Tg mice, with all three strains on the pure C57BL/6J genetic background. Fgfr4 KO mice on a mixed C57/129SvJ background were provided by Dr. Curtis Klaassen (University of Kansas Medical Center). Fgfr4/Shp double KO (Fgfr4/Shp DKO) mice were generated by cross breeding Fgfr4 KO and Shp KO mice. Egr1 KO mice on a C57BL/6 genetic background were obtained from Taconic (Hudson, NY). C57BL/6J mice bred in the same animal facility were used as wild-type (WT) controls for KO mice on C57BL/6J background. If KO mice were on a mixed genetic background (Fgfr4 KO and Fgfr4/Shp DKO), littermates were used as controls.