Chronic cholestatic liver diseases including primary sclerosing cholangitis (PSC) present a complex spectrum with regards to the cause, age of manifestation and histopathological features. Current treatment options are severely limited primarily due to a paucity of model systems mirroring the disease. Here, we describe the Keratin 5 (K5)-Cre; Klf5^fl/fl mouse that spontaneously develops severe liver disease during the postnatal period with features resembling PSC including a prominent ductular reaction, fibrotic obliteration of the bile ducts and secondary degeneration/necrosis of liver parenchyma. Over time, there is an expansion of Sox9⁺ hepatocytes in the damaged livers suggestive of a hepatocyte-mediated regenerative response. We conclude that Klf5 is required for the normal function of the hepatobiliary system and that the K5-Cre; Klf5^fl/fl mouse is an excellent model to probe the molecular events interlinking damage and regenerative response in the liver.

包括原发性硬化性胆管炎 (PSC) 在内的慢性胆汁淤积性肝病在病因、表现年龄和组织病理学特征方面呈现出复杂的谱系。当前的治疗选择受到严重限制，主要是由于缺乏反映该疾病的模型系统。在这里，我们描述了角蛋白 5 ( K5 ) -Cre；Klf5 ^fl/fl小鼠在出生后自发发展为严重肝病，其特征类似于 PSC，包括显着的导管反应、胆管纤维化闭塞和肝实质继发性变性/坏死。随着时间的推移，Sox9 ⁺受损肝脏中的肝细胞提示肝细胞介导的再生反应。我们得出结论，Klf5 是肝胆系统正常功能所必需的，而K5-Cre ; Klf5 ^fl/fl小鼠是探索肝脏损伤和再生反应相关分子事件的绝佳模型。