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

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: <i>d</i>o<i>u</i>ble resin <i>c</i>asting micro computed <i>t</i>omography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (<i>Jag1^Ndr/Ndr</i> 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 <i>Jag1^Ndr/Ndr</i> 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.