DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for Alagille syndrome

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Date
2021-02-26
Authors
Hankeová, Simona
Šalplachta, Jakub
Zikmund, Tomáš
Kavková, Michaela
Van Hul, Noemi
Břínek, Adam
Smékalová, Veronika
Lázňovský, Jakub
Dawit, Feven
Jaroš, Josef
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Mark
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ELIFE SCIENCES PUBLICATIONS LTD
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Abstract
Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models.
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Peer-reviewed
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en
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Creative Commons Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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