Mouse Model of Alagille Syndrome and Mechanisms of Jagged1 Missense Mutations.

ABSTRACT:

Background & aims

Alagille syndrome is a genetic disorder characterized by cholestasis, ocular abnormalities, characteristic facial features, heart defects, and vertebral malformations. Most cases are associated with mutations in JAGGED1 (JAG1), which encodes a Notch ligand, although it is not clear how these contribute to disease development. We aimed to develop a mouse model of Alagille syndrome to elucidate these mechanisms.

Methods

Mice with a missense mutation (H268Q) in Jag1 (Jag1^+/Ndr mice) were outbred to a C3H/C57bl6 background to generate a mouse model for Alagille syndrome (Jag1^Ndr/Ndr mice). Liver tissues were collected at different timepoints during development, analyzed by histology, and liver organoids were cultured and analyzed. We perfo

SUBMITTER: Andersson ER 

PROVIDER: S-EPMC7007299 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature