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Current Pathobiology Reports

, Volume 5, Issue 3, pp 233–241 | Cite as

Alagille Syndrome: Genetics and Functional Models

  • Melissa A. Gilbert
  • Nancy B. SpinnerEmail author
Pathobiology of Orphan Diseases (S Ranganathan, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pathobiology of Orphan Diseases

Abstract

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.

Keywords

Alagille syndrome Haploinsufficiency Gene therapy Liver disease Jagged1 Notch2 

Notes

Acknowledgements

We would like to thank Ellen Tsai, Kathy Loomes, Marcella Devoto, Ian Krantz, David Piccoli, and Binita Kamath for continued collaboration. We are grateful to the many people who have contributed to our understanding of the genetics of Alagille syndrome including Ian Krantz, Ray Colliton, Jennifer Morrissette, Dan Warthen, Ryan McDaniell, Rob Bauer, Laura Leonard, Christopher Grochowski, and Ramakrishnan Rajagopalan. Parts of this work were supported by R01DK081702.

Compliance with Ethical Standards

Conflict of Interest

Nancy Spinner reports a patent issued for Human Jagged1 Polypeptide Encoding Nucleic Acids and Methods.

Melissa Gilbert declares no conflicts of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory Medicine, 1012 Abramson Research CenterThe Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  2. 2.Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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