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Pathogenic variants of <jats:italic>DICER1<\/jats:italic> have been discovered in many rare cancers, including cystic liver tumors. However, the molecular mechanisms underlying liver lesions induced by these variants remain unclear. In the present study, we sought to gain a better understanding of the pathogenesis of these variants by generating a mouse model of liver\u2010specific DICER1 syndrome. The mouse model developed bile duct hyperplasia with fibrosis, similar to congenital hepatic fibrosis, as well as cystic liver tumors resembling those in Caroli's syndrome, intrahepatic cholangiocarcinoma, and hepatocellular carcinoma. Interestingly, the mouse model of DICER1 syndrome showed abnormal formation of primary cilia in the bile duct epithelium, which is a known cause of bile duct hyperplasia and cyst formation. These results indicated that <jats:italic>DICER1<\/jats:italic> mutations contribute to cystic liver tumors by inducing defective primary cilia. The mouse model generated in this study will be useful for elucidating the potential mechanisms of tumorigenesis induced by <jats:italic>DICER1<\/jats:italic> variants and for obtaining a comprehensive understanding of DICER1 syndrome. \u00a9 2024 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6320","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T04:21:23Z","timestamp":1719375683000},"page":"17-29","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Liver\u2010specific <scp>DICER1<\/scp> syndrome model mice develop cystic liver tumors with defective primary cilia"],"prefix":"10.1002","volume":"264","author":[{"given":"Keiki","family":"Oikawa","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology Tokyo Medical University  Tokyo 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