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CLONING AND GENERATION OF A MURINE MODEL OF GLYCEROL-3-PHOSPHATE DEHYDROGENASE 1-LIKE GENE, A CAUSE OF BRUGADA SYNDROME?

Michalec, Michael David (2007) CLONING AND GENERATION OF A MURINE MODEL OF GLYCEROL-3-PHOSPHATE DEHYDROGENASE 1-LIKE GENE, A CAUSE OF BRUGADA SYNDROME? Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Cardiovascular disease (CVD) is a major public health concern. It is the Nation's 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 patient's 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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Michalec, Michael Davidmdm10@pitt.edu,mmichalec@earthlink.netMDM10
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairFerrell, Robertrobert.ferrell@mail.hgen.pitt.eduRFERRELL
Committee MemberFeingold, Eleanoreleanor.feingold@mail.hgen.pitt.eduFEINGOLD
Committee MemberZhang, YingzeZhangY@upmc.eduZHANG3
Date: 27 June 2007
Date Type: Completion
Defense Date: 5 February 2007
Approval Date: 27 June 2007
Submission Date: 15 February 2007
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: CVD; molecular cloning; overexpression
Other ID: http://etd.library.pitt.edu/ETD/available/etd-02152007-144849/, etd-02152007-144849
Date Deposited: 10 Nov 2011 19:31
Last Modified: 19 Dec 2016 14:34
URI: http://d-scholarship.pitt.edu/id/eprint/6358

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