Date of Award:
5-2015
Document Type:
Thesis
Degree Name:
Master of Science (MS)
Department:
Animal, Dairy, and Veterinary Sciences
Committee Chair(s)
Zhongde Wang
Committee
Zhongde Wang
Committee
S. Clay Isom
Committee
Brian Gowen
Abstract
Atrial fibrillation (AF) and long QT syndrome (LQTS) are potentially lethal heart rhythm disorders that can be caused by mutations in the potassium channel gene KCNQ1. Middle East Respiratory Syndrome (MERS) is a viral infection with the potential to replicate the devastating effects of the SARS outbreak in 2003. All three of these diseases are in need of genetic animal models.
To address these needs, my thesis project focused on the development of genetic goat and hamster models of AF and LQTS, and genetic hamster models of MERS. Because of the goat’s similar organ size/physiology and the hamster’s similar lipid metabolism to that of humans, we believe that these animals will make better models of these diseases than more common animals.
Utilizing the gene-editing technology CRISPR/Cas9, I knocked out the KCNQ1 gene leading to a loss-of-function mutation known to cause LQTS, in goat and hamster cells. I also introduced a KCNQ1 gain-of-function mutation, known to cause AF, into hamster cells. These KCNQ1-edited cells are currently being used to develop animals susceptible to AF and/or LQTS for these heart diseases.
I also developed a DPP4 transgenic hamster in a STAT2 knockout background. The DPP4 transgene, encoding the human cell receptor for MERS virus entry, makes hamsters susceptible to MERS infection. The STAT2 knockout may increase disease severity, more closely mimicking the human disease. These hamsters may be ideal animal models for MERS. The models developed from this work will be used to develop life-saving treatments for these three diseases.
Checksum
fa0b72a929eba43f45d904495ef54656
Recommended Citation
Rasmussen, Dane A., "Development of Genetic Goat and Hamster Models of Atrial Fibrillation and Long QT Syndrome; and Genetic Hamster Models of Middle East Respiratory Syndrome" (2015). All Graduate Theses and Dissertations, Spring 1920 to Summer 2023. 4731.
https://digitalcommons.usu.edu/etd/4731
Included in
Animal Sciences Commons, Genetics Commons, Molecular Biology Commons
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