Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden; Department of Experimental Biology, Masaryk University, Brno, Czech Republic
Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden
Adam Brinek
CEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
Veronika Smekalova
CEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
Jakub Laznovsky
CEITEC – Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
Feven Dawit
Department of Pediatrics, Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Solna, Sweden
Josef Jaros
Department of Histology and Embryology, Masaryk University, Brno, Czech Republic
Department of Pediatrics, Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Solna, Sweden
Antal Nemeth
Department of Laboratory Medicine, Karolinska Institutet, Solna, Sweden
Björn Fischler
Department of Pediatrics, Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Karolinska University Hospital, Solna, Sweden
Department of Biosciences and Nutrition, Karolinska Institutet, Solna, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden
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.
