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

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Authors

HANKEOVÁ Simona ŠALPLACHTA Jakub ZIKMUND Tomáš KAVKOVÁ Michaela VAN HUL Noemi BŘÍNEK Adam SMÉKALOVÁ Veronika LÁZŇOVSKÝ Jakub DAWIT Feven JAROŠ Josef BRYJA Vítězslav LENDAHL Urban ELLIS Ewa NEMETH Antal FISCHLER Bjorn HANNEZO Edouard KAISER Jozef ANDERSSON Emma Rachel

Year of publication 2021
Type Article in Periodical
Magazine / Source eLife
MU Faculty or unit

Faculty of Science

Citation
Web https://elifesciences.org/articles/60916#xb0ffa41b
Doi http://dx.doi.org/10.7554/eLife.60916
Keywords PORTAL-VEIN; ARTERIOHEPATIC DYSPLASIA; HEPATIC-ARTERY; HUMAN JAGGED1; LIVER; MUTATIONS; INSIGHTS; NETWORK; ORGAN
Description 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 (Jag1(Ndr/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 Jag1(Ndr/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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