Cardiovascular disease (CVD) is a major public health concern. It is the Nations leading killer for both men and women of all racial and ethnic groups. CVD is responsible for about 1 million deaths each year in the United States. Health-related behaviors such as smoking, lack of physical activity and poor nutritional habits, as well as, many genetic factors contribute to its high incidence. Many of the genetic factors have been linked to high cholesterol, high blood pressure, obesity, diabetes and cardiac arrhythmias leading to stroke or sudden cardiac death. CVDs associated with ventricular arrhythmias are most severe. Among these is the Brugada syndrome also known as Sudden Unexpected Death Syndrome or SUDS. In 1992, the Brugada syndrome was classified as a distinct clinical heart condition characterized by an apparent right bundle branch block and ST segment elevation in the right precordial electrocardiogram (ECG) leads V1-V3. It is the most common cause of sudden cardiac death in South Asian men who are less than 50 years of age and have no underlying cardiac disease. Currently the only effective treatment for the disease is the Implantable Cardioverter Defibrillator (ICD) surgically placed in the patients chest. The genetic basis for the Brugada syndrome has been linked to mutations in the SCN5A gene that codes for the alpha-subunit of the cardiac sodium channel. Recently, a missense mutation has been discovered in a novel gene that causes the Brugada syndrome. The novel gene is named the Glycerol-3-phosphate Dehydrogenase 1-Like (GPD1L) gene. Preliminary studies suggest a direct relationship between the GPD1L mutation and a decrease in cellular sodium current. Transgenic murine models are useful tools for understanding the molecular function of novel genes. Transgenic constructs of the wild type and mutant GPD1L gene were generated and used for the production of transgenic mice. The mice were produced by pronuclear injection at the University of Pittsburgh Transgenic facility. These mice will provide an in vivo approach to study the GPD1L gene and create the first Brugada syndrome mouse model for cardiovascular disease studies.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-02152007-144849 |
| Date | 27 June 2007 |
| Creators | Michalec, Michael David |
| Contributors | Eleanor Feingold, Yingze Zhang, Robert Ferrell |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-02152007-144849/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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