{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:11:35Z","timestamp":1792678295753,"version":"4.5.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3134,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,2]]},"abstract":"\n \n \n The Notch signaling pathway is involved in determination of cell fate and control of cell proliferation in multiple organ systems.<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n encodes a ligand in the Notch pathway and has been identified as the disease-causing gene for the developmental disorder Alagille syndrome. Evidence from the study of human disease and mouse models has implicated<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n as having an important role in the development of bile ducts. We have derived a conditional knockout allele (<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n \n loxP) to study the role of<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n and Notch signaling in liver and bile duct development. We crossed<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n \n loxP mice with a transgenic line carrying Cre recombinase under the control of the albumin promoter and \u03b1-fetoprotein enhancer to ablate<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n in hepatoblasts. The liver-specific<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n conditional knockout mice showed normal bile duct development. To further decrease Notch pathway function, we crossed the<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n conditional knockout mice with mice carrying the hypomorphic<\/jats:bold>\n \n Notch2\n <\/jats:bold>\n allele, and bile duct anatomy remained normal. When<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n conditional mice were crossed with mice carrying the<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n null allele, the adult progeny exhibited striking bile duct proliferation.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n These results indicate that Notch signaling in the liver is sensitive to<\/jats:bold>\n \n Jag1\n <\/jats:bold>\n gene dosage and suggest a role for the Notch pathway in postnatal growth and morphogenesis of bile ducts.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.21460","type":"journal-article","created":{"date-parts":[[2007,1,5]],"date-time":"2007-01-05T20:47:45Z","timestamp":1168030065000},"page":"323-330","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":78,"title":["Bile duct proliferation in liver-specific Jag1 conditional knockout mice: Effects of gene dosage"],"prefix":"10.1097","volume":"45","author":[{"given":"Kathleen M.","family":"Loomes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Underkoffler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis","family":"Glover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gridley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus H.","family":"Kaestner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca J.","family":"Oakey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-10-20241201","doi-asserted-by":"crossref","first-page":"965973","DOI":"10.1242\/dev.01074","article-title":"Notch signaling: control of cell communication and cell fate.","volume":"131","author":"Lai","year":"2004","journal-title":"Development"},{"key":"R2-10-20241201","doi-asserted-by":"crossref","first-page":"438441","DOI":"10.1038\/74307","article-title":"Mutations in the human Delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis.","volume":"24","author":"Bulman","year":"2000","journal-title":"Nat Genet"},{"key":"R3-10-20241201","doi-asserted-by":"crossref","first-page":"707710","DOI":"10.1038\/383707a0","article-title":"Notch3 mutations in CADASIL, a hereditary 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