{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:43:48Z","timestamp":1740123828136,"version":"3.37.3"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transgenic Res"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 (<jats:italic>K5<\/jats:italic>)<jats:italic>-Cre<\/jats:italic>; <jats:italic>Klf5<\/jats:italic><jats:sup><jats:italic>fl\/fl<\/jats:italic><\/jats:sup> 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<jats:sup>+<\/jats:sup> 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 <jats:italic>K5-Cre<\/jats:italic>; <jats:italic>Klf5<\/jats:italic><jats:sup><jats:italic>fl\/fl<\/jats:italic><\/jats:sup> mouse is an excellent model to probe the molecular events interlinking damage and regenerative response in the liver.<\/jats:p>","DOI":"10.1007\/s11248-021-00267-6","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T18:02:15Z","timestamp":1623434535000},"page":"701-707","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Severe liver disease resembling PSC in mice with K5-Cre mediated deletion of Kr\u00fcppel-like factor 5 (Klf5)"],"prefix":"10.1007","volume":"30","author":[{"given":"\u00c5sa","family":"Bergstr\u00f6m","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Gerling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"No\u00e9mi","family":"Van Hul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Fern\u00e1ndez Moro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Rozell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rune","family":"Toftg\u00e5rd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5787-1040","authenticated-orcid":false,"given":"Inderpreet","family":"Sur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"267_CR1","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.jid.2016.09.026","volume":"137","author":"M Devos","year":"2017","unstructured":"Devos M et al (2017) Elevated DeltaNp63alpha levels facilitate epidermal and biliary oncogenic transformation. J Invest Dermatol 137:494\u2013505. https:\/\/doi.org\/10.1016\/j.jid.2016.09.026","journal-title":"J Invest Dermatol"},{"key":"267_CR2","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1053\/j.gastro.2005.10.018","volume":"130","author":"P Fickert","year":"2006","unstructured":"Fickert P et al (2006) 24-norUrsodeoxycholic acid is superior to ursodeoxycholic acid in the treatment of sclerosing cholangitis in Mdr2 (Abcb4) knockout mice. Gastroenterology 130:465\u2013481. https:\/\/doi.org\/10.1053\/j.gastro.2005.10.018","journal-title":"Gastroenterology"},{"key":"267_CR3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1208651109","author":"Y Fujii","year":"2012","unstructured":"Fujii Y et al (2012) CDX1 confers intestinal phenotype on gastric epithelial cells via induction of stemness-associated reprogramming factors SALL4 and KLF5. Proc Natl Acad Sci USA. https:\/\/doi.org\/10.1073\/pnas.1208651109","journal-title":"Proc Natl Acad Sci USA"},{"key":"267_CR4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.17462","author":"S Hayashi","year":"2016","unstructured":"Hayashi S, Manabe I, Suzuki Y, Relaix F, Oishi Y (2016) Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice. Elife. https:\/\/doi.org\/10.7554\/eLife.17462","journal-title":"Elife"},{"key":"267_CR5","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/gb-2003-4-2-206","volume":"4","author":"J Kaczynski","year":"2003","unstructured":"Kaczynski J, Cook T, Urrutia R (2003) Sp1- and Kruppel-like transcription factors. 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J Clin Invest 120:254\u2013265. https:\/\/doi.org\/10.1172\/JCI40295","journal-title":"J Clin Invest"}],"container-title":["Transgenic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11248-021-00267-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11248-021-00267-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11248-021-00267-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T14:18:19Z","timestamp":1632838699000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11248-021-00267-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,11]]},"references-count":12,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["267"],"URL":"https:\/\/doi.org\/10.1007\/s11248-021-00267-6","relation":{},"ISSN":["0962-8819","1573-9368"],"issn-type":[{"type":"print","value":"0962-8819"},{"type":"electronic","value":"1573-9368"}],"subject":[],"published":{"date-parts":[[2021,6,11]]},"assertion":[{"value":"16 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}