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	https://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.