ArticleHepatology (Baltimore, Md.)2016
Jagged1 heterozygosity in mice results in a congenital cholangiopathy which is reversed by concomitant deletion of one copy of Poglut1 (Rumi).
Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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49 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Sex differences and risk factors for bleeding in Alagille syndrome.EMBO molecular medicine · 2022Pooled it
- Antisense oligonucleotide-mediated upregulation ofMolecular therapy. Nucleic acids · 2025Article
- Adeno-associated Virus-mediated Silencing of Sox4 Leads to Long-Term Amelioration of Liver Phenotypes in Mouse Models of Alagille Syndrome.Gastroenterology · 2025Article
- Phenotypic Divergence of JAG1- and NOTCH2-Associated Alagille Syndrome & Disease-Specific NOTCH2 Variant Classification Guidelines.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- The glycosyltransferase POGLUT1 regulates muscle stem cell development and maintenance in mice.PLoS genetics · 2025Article
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- Liver oval cells in response to HDAC1 inhibitor trichostatin A: immunohistochemical characterization using OV-6 hepatic expression.Anatomy & cell biology · 2025Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- The glycosyltransferase POGLUT1 regulates muscle stem cell development and maintenance in mice.bioRxiv : the preprint server for biology · 2024Article
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- Regenerative failure of intrahepatic biliary cells in Alagille syndrome rescued by elevated Jagged/Notch/Sox9 signaling.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Role of YAP1 Signaling in Biliary Development, Repair, and Disease.Seminars in liver disease · 2022Review
- Role of Immune Cells in Biliary Repair.Frontiers in immunology · 2022Review
- The developmental origins of Notch-driven intrahepatic bile duct disorders.Disease models & mechanisms · 2021Article
- Notch-Jagged signaling complex defined by an interaction mosaic.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Compensatory hepatic adaptation accompanies permanent absence of intrahepatic biliary network due to YAP1 loss in liver progenitors.Cell reports · 2021Article
- Review
- Current Views on the Roles ofBiomolecules · 2021Review
- Overexpressed miR-335-5p reduces atherosclerotic vulnerable plaque formation in acute coronary syndrome.Journal of clinical laboratory analysis · 2021Article
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7 authors at 3 institutions in 1 country.
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Abstract
unlabelledHaploinsufficiency for the Notch ligand JAG1 in humans results in an autosomal-dominant, multisystem disorder known as Alagille syndrome, which is characterized by a congenital cholangiopathy of variable severity. Here, we show that on a C57BL/6 background, jagged1 heterozygous mice (Jag1(+/-) ) exhibit impaired intrahepatic bile duct (IHBD) development, decreased SOX9 expression, and thinning of the periportal vascular smooth muscle cell (VSMC) layer, which are apparent at embryonic day 18 and the first postnatal week. In contrast, mice double heterozygous for Jag1 and the glycosyltransferase, Poglut1 (Rumi), start showing a significant improvement in IHBD development and VSMC differentiation during the first week. At P30, Jag1(+/-) mice show widespread ductular reactions and ductopenia in liver and a mild, but statistically, significant bilirubinemia. In contrast, P30 Jag1/Rumi double-heterozygous mice show well-developed portal triads around most portal veins, with no elevation of serum bilirubin. Conditional deletion of Rumi in VSMCs results in progressive arborization of the IHBD tree, whereas deletion of Rumi in hepatoblasts frequently results in an increase in the number of hepatic arteries without affecting bile duct formation. Nevertheless, removing one copy of Rumi from either VSMCs or hepatoblasts is sufficient to partially suppress the Jag1(+/-) bile duct defects. Finally, all Rumi target sites of the human JAG1 are efficiently glucosylated, and loss of Rumi in VSMCs results in increased levels of full-length JAG1 and a shorter fragment of JAG1 without affecting Jag1 messenger RNA levels.
conclusionsOn a C57BL/6 background, Jag1 haploinsufficiency results in bile duct paucity in mice. Removing one copy of Rumi suppresses the Jag1(+/-) bile duct phenotype, indicating that Rumi opposes JAG1 function in the liver.
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