Translational Research in a Large Animal Model of Angelman Syndrome
Dr. Scott Dindot presented a project funded by FAST to develop a large animal model of Angelman Syndrome. The project aims to understand the pathophysiology of the condition and test potential therapies using pigs as a preclinical model. The pig model exhibits phenotypes similar to those seen in patients, including altered neonatal behavior, severe hypotonia, uncoordinated movement, altered brain development, and spontaneous seizures. The pigs also show reduced vocalization, which could serve as a biomarker for testing therapies. The model provides a unique opportunity to study the condition and develop new treatments. The project is a collaborative effort involving multiple researchers and institutions.
In this talk, I will provide an overview of a project funded by FAST to develop a large animal model of Angelman Syndrome. I will explain the importance of animal models in research and discuss the specific reasons for choosing a pig model. Additionally, I will highlight the phenotypes observed in the pig model and the potential applications for testing therapies.
The Role of Animal Models in Research
Animal models play a crucial role in understanding the pathophysiology of a condition. They allow researchers to conduct experiments that are not possible in humans and provide valuable insights into the genetics and management of the condition. In the case of Angelman Syndrome, there are several animal models available, including mouse, rat, and pig models. Each model serves a specific purpose and contributes to our understanding of the condition.
The Pig Model of Angelman Syndrome
The pig model of Angelman Syndrome was developed using CRISPR-Cas9 technology, which allows precise genetic modifications. Pigs were chosen as a model because they share many similarities with humans, both genetically and behaviorally. Pigs are highly intelligent animals and exhibit complex vocalization patterns, making them suitable for studying the communication deficits observed in Angelman Syndrome. Additionally, pigs have advanced development at birth, allowing researchers to study early neurodevelopmental aspects of the condition.
Phenotypes Observed in the Pig Model
The pig model of Angelman Syndrome exhibits several phenotypes that mirror those observed in patients. These include altered neonatal behavior, severe hypotonia (poor muscle tone), uncoordinated movement, stilted gait, reduced vocalization, altered brain development, and spontaneous seizures. These phenotypes provide valuable insights into the pathophysiology of Angelman Syndrome and can be used to test potential therapies.
Potential Applications for Testing Therapies
The pig model of Angelman Syndrome serves as an ideal preclinical model for testing therapies. Researchers can administer treatments to the pigs at a young age, mimicking the conditions in human patients. The large size of the pigs allows for the collection of ample biofluids, which can be used for biomarker discovery. Additionally, the pig model can be used to assess the efficacy of different therapies and determine the optimal therapeutic window for treatment.
The pig model of Angelman Syndrome provides a unique opportunity to study the pathophysiology of the condition and test potential therapies. The phenotypes observed in the pig model closely resemble those seen in patients, making it a valuable tool for translational research. The development of this model would not have been possible without the collaborative efforts of researchers, facilities, and support from organizations like FAST.
- Title: Translational Research in a Large Animal Model of Angelman Syndrome
- Author(s): Scott Dindot
- Author(s)’ affiliation: Texas A&M University; Ultragenyx Pharmaceutical
- Publication date: 2022-01-04
- Collection: 2021 FAST Science Summit