Characteristics of the Ube3a Large Deletion Rat (Legend-Rat)

Quick Overview

In this panel discussion at the 2018 FAST Science Summit, researchers present the characteristics of the Ube3a Large Deletion Rat (Legend-Rat), a rat model of Angelman Syndrome. The rat model was developed by the FAST-FIRE team and has been characterized over the past two years. The researchers discuss the importance of having a higher-level model to test drugs and show behavioral changes with therapeutics. They highlight the characteristics of the rat model, including synaptic transmission, synaptic plasticity, gait abnormalities, ultrasonic vocalizations, motor activity, and EEG patterns. The researchers also discuss the potential for using the rat model in preclinical studies and the importance of the Angelman Syndrome registry for gathering information on patients.

Introduction

In this talk, we will be discussing the characteristics of the Ube3a Large Deletion Rat, also known as the Legend-Rat. This rat model of Angelman Syndrome was developed by the FAST-FIRE team and has been extensively characterized over the past two years. The rat model provides a higher level model for testing drugs and studying behavioral changes, which is crucial for further drug development.

Speakers

The panel of speakers for this talk includes Dr. Edwin Weeber from the University of South Florida, Dr. Jill Silverman from UC Davis, and Dr. Anne Anderson from Texas Children’s Hospital and Baylor College of Medicine. Each speaker will discuss different aspects of the rat model and its characteristics.

Synaptic Function and Gait Analysis

Dr. Edwin Weeber begins the talk by discussing the synaptic function and gait analysis of the Legend-Rat. He explains how electrophysiology is used to study synaptic connections in the rat’s hippocampus, which is important for learning and memory. The rat model shows differences in synaptic transmission and plasticity compared to wild type rats. Dr. Weeber also demonstrates the use of DigiGait, a computerized system that measures the rat’s gait and provides quantitative data on motor function.

Behavior and Ultrasonic Vocalizations

Dr. Jill Silverman focuses on the behavior of the Legend-Rat, particularly its ultrasonic vocalizations. She explains that rats use ultrasonic vocalizations to communicate with their mothers when they are separated or in need of assistance. The rat model shows a decrease in ultrasonic vocalizations compared to wild type rats. Dr. Silverman also discusses other behavioral tests, such as motor activity and learning tasks using iPads, which show deficits in the Legend-Rat.

EEG and Epilepsy

Dr. Anne Anderson discusses the EEG and epilepsy characteristics of the Legend-Rat. She explains that the rat model shows an increase in slow wave activity, known as delta power, which is a characteristic feature of Angelman Syndrome in humans. The rat model also exhibits seizures and epileptiform activity when stimulated with chemoconvulsants or audiogenic stimulation. Dr. Anderson emphasizes the importance of EEG monitoring to further understand the seizure activity and sleep patterns in the rat model.

Conclusion and Future Directions

The speakers conclude the talk by highlighting the similarities between the Legend-Rat and Angelman Syndrome in humans. They emphasize the importance of using the rat model for preclinical studies and drug development. They also encourage families to participate in the Angelman Syndrome registry and seek care at comprehensive Angelman clinics to contribute to research and clinical trials.

Questions and Answers

During the Q&A session, the speakers address questions about the effectiveness of treatments in rats compared to humans, the variability of treatments for different individuals, and the presence of audiogenic seizures in humans with Angelman Syndrome. They also discuss the importance of gathering information from families who do not have access to Angelman clinics and suggest participating in the global registry as a way to contribute valuable data.

Overall, the talk provides valuable insights into the characteristics of the Ube3a Large Deletion Rat and its potential for advancing research and drug development for Angelman Syndrome.