Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice
The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 h...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2005-03, Vol.41 (3), p.487-496 |
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| container_title | Hepatology (Baltimore, Md.) |
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| creator | CROQUELOIS, Adrien BLINDENBACHER, Alex TERRACCIANO, Luigi XUEYA WANG LANGER, Igor RADTKE, Freddy HEIM, Markus H |
| description | The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype. We have previously generated mice with inducible Notch1 disruption using an interferon-inducible Cre-recombinase transgene in combination with the loxP flanked Notch1 gene. We used this conditional Notch1 knockout mouse model to investigate the role of Notch1 signaling in liver cell proliferation and differentiation. Deletion of Notch1 did not result in bile duct paucity, but, surprisingly, resulted in a continuous proliferation of hepatocytes. In conclusion, within weeks after Notch1 inactivation, the mice developed nodular regenerative hyperplasia without vascular changes in the liver. |
| doi_str_mv | 10.1002/hep.20571 |
| format | Article |
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The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype. We have previously generated mice with inducible Notch1 disruption using an interferon-inducible Cre-recombinase transgene in combination with the loxP flanked Notch1 gene. We used this conditional Notch1 knockout mouse model to investigate the role of Notch1 signaling in liver cell proliferation and differentiation. Deletion of Notch1 did not result in bile duct paucity, but, surprisingly, resulted in a continuous proliferation of hepatocytes. In conclusion, within weeks after Notch1 inactivation, the mice developed nodular regenerative hyperplasia without vascular changes in the liver.</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.20571</identifier><identifier>PMID: 15723439</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken, NJ: Wiley</publisher><subject>Animals ; Biological and medical sciences ; Calcium-Binding Proteins ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Cell Proliferation ; Focal Nodular Hyperplasia - etiology ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Hepatectomy ; Hepatocytes - pathology ; Intercellular Signaling Peptides and Proteins ; Jagged-1 Protein ; Liver Regeneration ; Liver. Bile. Biliary tracts ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Membrane Proteins ; Mice ; Mice, Inbred C57BL ; Molecular and cellular biology ; Other diseases. Semiology ; Proteins - genetics ; Proteins - physiology ; Serrate-Jagged Proteins ; Signal Transduction - physiology ; Vertebrates: digestive system</subject><ispartof>Hepatology (Baltimore, Md.), 2005-03, Vol.41 (3), p.487-496</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c273t-77016703a488592c3a25dfde019cc22bcdee8e9592ea3c68dbfb7c925adc8cb53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16655590$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15723439$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CROQUELOIS, Adrien</creatorcontrib><creatorcontrib>BLINDENBACHER, Alex</creatorcontrib><creatorcontrib>TERRACCIANO, Luigi</creatorcontrib><creatorcontrib>XUEYA WANG</creatorcontrib><creatorcontrib>LANGER, Igor</creatorcontrib><creatorcontrib>RADTKE, Freddy</creatorcontrib><creatorcontrib>HEIM, Markus H</creatorcontrib><title>Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype. We have previously generated mice with inducible Notch1 disruption using an interferon-inducible Cre-recombinase transgene in combination with the loxP flanked Notch1 gene. We used this conditional Notch1 knockout mouse model to investigate the role of Notch1 signaling in liver cell proliferation and differentiation. Deletion of Notch1 did not result in bile duct paucity, but, surprisingly, resulted in a continuous proliferation of hepatocytes. In conclusion, within weeks after Notch1 inactivation, the mice developed nodular regenerative hyperplasia without vascular changes in the liver.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium-Binding Proteins</subject><subject>Cell differentiation, maturation, development, hematopoiesis</subject><subject>Cell physiology</subject><subject>Cell Proliferation</subject><subject>Focal Nodular Hyperplasia - etiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Hepatectomy</subject><subject>Hepatocytes - pathology</subject><subject>Intercellular Signaling Peptides and Proteins</subject><subject>Jagged-1 Protein</subject><subject>Liver Regeneration</subject><subject>Liver. Bile. Biliary tracts</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Membrane Proteins</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular and cellular biology</subject><subject>Other diseases. Semiology</subject><subject>Proteins - genetics</subject><subject>Proteins - physiology</subject><subject>Serrate-Jagged Proteins</subject><subject>Signal Transduction - physiology</subject><subject>Vertebrates: digestive system</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0E1Lw0AQBuBFFK3Vg39A9qLgIXU_stnsUYofhaIe9Bw2k4ldyZe7SaH_3mgDPc1hnnlhXkKuOFtwxsT9BruFYErzIzLjSuhISsWOyYwJzSLDpTkj5yF8M8ZMLNJTcsaVFjKWZkbeV00xgMsrpK6x0Lut7V3b0Lakr20PG07BDgEDbdpiqKynHr-wQT-qLdLNrkPfVTY4O57T2gFekJPSVgEvpzknn0-PH8uXaP32vFo-rCMQWvaR1ownmkkbp6kyAqQVqigLZNwACJFDgZiiGVdoJSRpkZe5BiOULSCFXMk5ud3ndr79GTD0We0CYFXZBtshZImOE8XHJ-fkbg_BtyF4LLPOu9r6XcZZ9ldfNtaX_dc32uspdMhrLA5y6msENxOwAWxVetuACweXJEopw-Qv0Ah4xg</recordid><startdate>20050301</startdate><enddate>20050301</enddate><creator>CROQUELOIS, Adrien</creator><creator>BLINDENBACHER, Alex</creator><creator>TERRACCIANO, Luigi</creator><creator>XUEYA WANG</creator><creator>LANGER, Igor</creator><creator>RADTKE, Freddy</creator><creator>HEIM, Markus H</creator><general>Wiley</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20050301</creationdate><title>Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice</title><author>CROQUELOIS, Adrien ; BLINDENBACHER, Alex ; TERRACCIANO, Luigi ; XUEYA WANG ; LANGER, Igor ; RADTKE, Freddy ; HEIM, Markus H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c273t-77016703a488592c3a25dfde019cc22bcdee8e9592ea3c68dbfb7c925adc8cb53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Calcium-Binding Proteins</topic><topic>Cell differentiation, maturation, development, hematopoiesis</topic><topic>Cell physiology</topic><topic>Cell Proliferation</topic><topic>Focal Nodular Hyperplasia - etiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hepatectomy</topic><topic>Hepatocytes - pathology</topic><topic>Intercellular Signaling Peptides and Proteins</topic><topic>Jagged-1 Protein</topic><topic>Liver Regeneration</topic><topic>Liver. Bile. Biliary tracts</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Membrane Proteins</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Molecular and cellular biology</topic><topic>Other diseases. Semiology</topic><topic>Proteins - genetics</topic><topic>Proteins - physiology</topic><topic>Serrate-Jagged Proteins</topic><topic>Signal Transduction - physiology</topic><topic>Vertebrates: digestive system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CROQUELOIS, Adrien</creatorcontrib><creatorcontrib>BLINDENBACHER, Alex</creatorcontrib><creatorcontrib>TERRACCIANO, Luigi</creatorcontrib><creatorcontrib>XUEYA WANG</creatorcontrib><creatorcontrib>LANGER, Igor</creatorcontrib><creatorcontrib>RADTKE, Freddy</creatorcontrib><creatorcontrib>HEIM, Markus H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CROQUELOIS, Adrien</au><au>BLINDENBACHER, Alex</au><au>TERRACCIANO, Luigi</au><au>XUEYA WANG</au><au>LANGER, Igor</au><au>RADTKE, Freddy</au><au>HEIM, Markus H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2005-03-01</date><risdate>2005</risdate><volume>41</volume><issue>3</issue><spage>487</spage><epage>496</epage><pages>487-496</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>The discovery that the human Jagged1 gene (JAG1) is the Alagille syndrome disease gene indicated that Notch signaling has an important role in bile duct homeostasis. The functional study of this signaling pathway has been difficult because mice with targeted mutations in Jagged1, Notch1, or Notch2 have an embryonic lethal phenotype. We have previously generated mice with inducible Notch1 disruption using an interferon-inducible Cre-recombinase transgene in combination with the loxP flanked Notch1 gene. We used this conditional Notch1 knockout mouse model to investigate the role of Notch1 signaling in liver cell proliferation and differentiation. Deletion of Notch1 did not result in bile duct paucity, but, surprisingly, resulted in a continuous proliferation of hepatocytes. In conclusion, within weeks after Notch1 inactivation, the mice developed nodular regenerative hyperplasia without vascular changes in the liver.</abstract><cop>Hoboken, NJ</cop><pub>Wiley</pub><pmid>15723439</pmid><doi>10.1002/hep.20571</doi><tpages>10</tpages></addata></record> |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE; EZB Electronic Journals Library |
| subjects | Animals Biological and medical sciences Calcium-Binding Proteins Cell differentiation, maturation, development, hematopoiesis Cell physiology Cell Proliferation Focal Nodular Hyperplasia - etiology Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Hepatectomy Hepatocytes - pathology Intercellular Signaling Peptides and Proteins Jagged-1 Protein Liver Regeneration Liver. Bile. Biliary tracts Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Membrane Proteins Mice Mice, Inbred C57BL Molecular and cellular biology Other diseases. Semiology Proteins - genetics Proteins - physiology Serrate-Jagged Proteins Signal Transduction - physiology Vertebrates: digestive system |
| title | Inducible inactivation of Notch1 causes nodular regenerative hyperplasia in mice |
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