Update on Angelman Syndrome Human iPSC Biorepository Project and the Angelman Syndrome Large Deletion Mouse Model
This summary provides an update on the Angelman Syndrome Human iPSC Biorepository Project and the Angelman Syndrome Large Deletion Mouse Model. The project aims to create a panel of Angelman iPSC cell lines from patients and distribute them to investigators for research purposes. So far, 12 cell lines have been generated, covering various genotypes. The project also involves the creation of mouse models to mimic the 5 to 6 megabase deletion seen in 70% of Angelman patients. The researchers have successfully engineered mice with deletions and are working on generating pure germline transmission for further study. The project is a collaborative effort involving the Yale Stem Cell Center, Yale Genome Center, and the researcher’s own lab.
In this talk, we provide an update on the progress of the Angelman Syndrome Human iPSC Biorepository Project and the Angelman Syndrome Large Deletion Mouse Model. These projects aim to advance our understanding of Angelman Syndrome and provide valuable resources for research and potential treatments.
Angelman Syndrome is a genetic disorder caused by the loss of function of the UBE3A gene. This gene is typically expressed from the mother’s chromosome, while the father’s chromosome remains silent. Animal models have been instrumental in studying the syndrome, but there are limitations to their applicability to human brains. To overcome this, the use of induced pluripotent stem cells (iPSCs) has emerged as a promising alternative.
Angelman Syndrome Human iPSC Biorepository Project
The goal of the Angelman Syndrome Human iPSC Biorepository Project is to create a panel of Angelman iPSC cell lines from patients. This project aims to cover various genotypes, including larger deletions, UBE3A point mutations, UPD, imprinting defects, and UBE3A gain-of-function mutations. The project also includes a normal control group.
To create these cell lines, blood samples from Angelman patients are collected and shipped to the Yale stem cell laboratory. Using specialized techniques, the blood cells are converted into iPSCs, which can then be differentiated into brain cells for further study. So far, 12 cell lines have been generated, covering a range of genotypes.
The project also focuses on distributing these cell lines to researchers and pharmaceutical companies worldwide, allowing them to study Angelman Syndrome and develop potential treatments. Some cell lines have already been distributed, and the project aims to generate more cell lines in the future.
Angelman Syndrome Large Deletion Mouse Model
The Angelman Syndrome Large Deletion Mouse Model project aims to create a mouse model that closely mimics the 5 to 6 megabase deletions found in 70% of Angelman patients. While several mouse models exist, they do not fully replicate this specific genotype.
Using the CRISPR Cas9 technique, researchers are working to engineer mice with the desired deletions. The project involves multiple steps of molecular engineering and breeding to achieve the desired results. The first mouse model with the larger deletion has been successfully generated, and efforts are underway to establish a pure germline transmission. The second mouse model, which disrupts specific regions while keeping the UBE3A gene intact, is also in progress.
These mouse models will provide valuable tools for studying the pathophysiology of Angelman Syndrome and testing potential treatments.
The progress of these projects would not be possible without the collaboration and support of various individuals and institutions. The author would like to thank Allyson Brett and the board of directors for their guidance and support. Special thanks are also extended to Barbara Bailus for her continued support as the chief science officer.
The author expresses gratitude to the participating families for their contributions to the projects, despite the challenges posed by the COVID-19 pandemic. The author also acknowledges the support of the Yale Stem Cell Center, the Yale Genome Center, and the transgenic core facility for their technical expertise and assistance.
Finally, the author recognizes the hard work and dedication of the research team, including Cindy Bao, Quinn Young, Caihong Qiu, Jason, Sun Wing, Cassandra, and Sean Na, who have contributed to the success of these projects.
The Angelman Syndrome Human iPSC Biorepository Project and the Angelman Syndrome Large Deletion Mouse Model are making significant progress in advancing our understanding of Angelman Syndrome. The creation of iPSC cell lines and mouse models will provide valuable resources for researchers and pave the way for further research and potential treatments. The author expresses gratitude to all those involved and looks forward to future developments in these projects.
- Title: Update on Angelman Syndrome Human iPSC Biorepository Project and the Angelman Syndrome Large Deletion Mouse Model
- Author(s): Yong-Hui Jiang
- Author(s)’ affiliation: Yale School of Medicine
- Publication date: 2022-01-04
- Collection: 2021 FAST Science Summit