Creating a Transgenic Goat Model of Familial Lone Atrial Fibrillation

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Zhongde Wang


Atrial fibrillation is one of the most common forms of cardiac arrhythmia affecting about 2.3 million people in the U.S. It can lead to a variety of conditions such as thromboembolism, heart failure, and ventricular arrhythmia. These types of conditions can result in death. Though there are many risk factors, AF can be hereditary (lone AF). Many KCNQ1 gain-of-function mutations have been associated with lone AF development, though their effects have only been tested in cultured animal cells and mouse models. Because their organ sizes and physiology are similar to humans, a large animal model of these mutations will greatly advance the study of this disease by providing a more realistic simulation of AF than previous small animal models. The goal of this project is to create the first transgenic goat model of lone AF by inducing the human KCNQ1 mutations S140G, V141M, and Q147R. We have successfully designed and constructed CRISPR vectors targeting an area where these three mutations exist.

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