Title of Oral/Poster Presentation

Creating Genetically Engineered Hamster Models of Atrial Fibrillation and Long QT Syndrome

Presenter Information

Dane RasmussenFollow

Class

Article

Department

Animal, Dairy, and Veterinary Sciences

Faculty Mentor

Zhongde Wang

Presentation Type

Oral Presentation

Abstract

Atrial fibrillation (AF) and long QT syndrome (LQT) are two leading heart diseases, both of which can be caused by genetic mutations in the KCNQ1 gene. Both conditions can be fatal if left untreated. KCNQ1 codes for a potassium channel subunit in cardiomyocytes responsible for heart repolarization. Many gain-of-function mutations in this gene have been known to cause AF, while loss-of-function mutations cause LQT. By inducing a mutation in the KCNQ1 gene that causes AF or LQT in humans into the hamster genome, we would be able to study these diseases in an effective model organism that has shown to have advantages over other small organisms such as mice. The goal of this research is to create hamster models of AF and LQT by inducing the most prevalent human KCNQ1-mutations into their genomes. We first subcloned and characterized the hamster genomic locus harboring exon 2 of the KCNQ1 gene that corresponds to the human KCNQ1 coding sequence, where AF and LQT-causing mutations occur. Utilizing CRISPR/Cas9 genome editing technology, we have induced a KCNQ1 knockout mutation in hamsters at the cellular level. Experiments to induce the AF-inducing point mutation, Q147R, are also being performed. Establishing cell lines of these modified genomes will provide excellent in vitro models of these heart diseases. Ultimately, the CRISPR/Cas9 technology used to modify these cells will be used created live animals containing these heart disease mutations providing critically needed models of atrial fibrillation and long QT syndrome.

Start Date

4-9-2015 11:00 AM

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Apr 9th, 11:00 AM

Creating Genetically Engineered Hamster Models of Atrial Fibrillation and Long QT Syndrome

Atrial fibrillation (AF) and long QT syndrome (LQT) are two leading heart diseases, both of which can be caused by genetic mutations in the KCNQ1 gene. Both conditions can be fatal if left untreated. KCNQ1 codes for a potassium channel subunit in cardiomyocytes responsible for heart repolarization. Many gain-of-function mutations in this gene have been known to cause AF, while loss-of-function mutations cause LQT. By inducing a mutation in the KCNQ1 gene that causes AF or LQT in humans into the hamster genome, we would be able to study these diseases in an effective model organism that has shown to have advantages over other small organisms such as mice. The goal of this research is to create hamster models of AF and LQT by inducing the most prevalent human KCNQ1-mutations into their genomes. We first subcloned and characterized the hamster genomic locus harboring exon 2 of the KCNQ1 gene that corresponds to the human KCNQ1 coding sequence, where AF and LQT-causing mutations occur. Utilizing CRISPR/Cas9 genome editing technology, we have induced a KCNQ1 knockout mutation in hamsters at the cellular level. Experiments to induce the AF-inducing point mutation, Q147R, are also being performed. Establishing cell lines of these modified genomes will provide excellent in vitro models of these heart diseases. Ultimately, the CRISPR/Cas9 technology used to modify these cells will be used created live animals containing these heart disease mutations providing critically needed models of atrial fibrillation and long QT syndrome.