Alagille syndrome: Genetics and Functional Models.

Purpose of review: We review the genetics of the autosomal dominant, multi-system disorder, Alagille syndrome and provide a summary on how current functional models and emerging biotechnologies are equipped to guide scientists towards novel therapies. The importance of haploinsufficiency as a disease mechanism will be underscored throughout this discussion.

Recent findings: Alagille syndrome, a human disorder affecting the liver, heart, vasculature, kidney, and other systems, is caused by mutations in the Notch signaling pathway ligand, Jagged1 ( JAG1 ) or the receptor, NOTCH2 . Current advances in animal modeling, in vitro cell culture, and human induced pluripotent stem cells, provide new opportunities in which to study disease mechanisms and manifestations.

Summary: We anticipate that the availability of innovative functional models will allow scientists to test new gene therapies or small molecule treatments in physiologically-relevant systems. With these advances, we look forward to the development of new methods to help Alagille syndrome patients.