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However,\n                      <jats:italic>Fxr<\/jats:italic>\n                      \u2010deficient mice do not develop early\u2010onset liver disease, possibly due to the predominance of hydrophilic muricholic acids (MCAs) in their BA pool. Mice lacking\n                      <jats:italic>Cyp2c70<\/jats:italic>\n                      display a human\u2010like BA composition, lacking MCAs. This study aimed to evaluate whether\n                      <jats:italic>Fxr\/Cyp2c70\u2010<\/jats:italic>\n                      double knockout (DKO) mice recapitulate the pathophysiology of human FXR\u2010deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      BA metabolism and liver pathology were assessed in wild\u2010type (WT),\n                      <jats:italic>Fxr<\/jats:italic>\n                      \u2010knockout (KO),\n                      <jats:italic>Cyp2c70<\/jats:italic>\n                      \u2010KO and DKO mice of both sexes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Fxr<\/jats:italic>\n                      \u2010deficiency markedly reduced the amounts of bile salt export pump (BSEP\/ABCB11), but did not affect biliary BA secretion. DKO mice showed exacerbated hepatocytic injury and inflammation compared to\n                      <jats:italic>Fxr<\/jats:italic>\n                      \u2010KO mice of both sexes. Surprisingly, despite higher alanine aminotransferase levels that indicate hepatocellular damage, female DKO mice showed much less liver fibrosis and ductular reactions than female\n                      <jats:italic>Cyp2c70<\/jats:italic>\n                      \u2010KO mice. Gene Set Enrichment Analysis suggested that epithelial\u2013mesenchymal transition was upregulated in\n                      <jats:italic>Cyp2c70<\/jats:italic>\n                      \u2010KO livers compared to WT mice but downregulated particularly in livers of female DKO mice compared to\n                      <jats:italic>Cyp2c70<\/jats:italic>\n                      \u2010KO. Biliary BA hydrophobicity was increased by the deletion of\n                      <jats:italic>Cyp2c70<\/jats:italic>\n                      , yet reduced by simultaneous absence of\n                      <jats:italic>Fxr<\/jats:italic>\n                      in female mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Fxr\/Cyp2c70<\/jats:italic>\n                      \u2010DKO mice exhibit more severe hepatocytic injury than\n                      <jats:italic>Fxr<\/jats:italic>\n                      \u2010KO mice, mirroring the clinical phenotype of FXR deficiency. These data highlight the importance of studying the aetiology of cholestatic liver diseases in the context of a human\u2010like BA composition.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70632","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T13:11:51Z","timestamp":1775740311000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Farnesoid x Receptor Deficiency Promotes Hepatocytic Injury in\n                    <i>Cyp2c70<\/i>\n                    \u2010Deficient Mice With a Human\u2010Like Bile Acid Composition"],"prefix":"10.1111","volume":"46","author":[{"given":"Hilde D.","family":"de Vries","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Groningen, University Medical Center Groningen (UMCG)  Groningen the 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