ExeGen SCN5A +/E558XMiniswine
Sudden arrhythmia death syndromes (SADS) are genetic heart rhythm abnormalities that can cause sudden death in young, apparently healthy people. Each year in the United States, approximately 295,000 Americans die suddenly and unexpectedly due to cardiac arrhythmias. Almost 4,000 of them are young people under age 35. The conditions that are considered SADS include but are not limited to Long QT Syndrome, Hypertrophic Cardiomyopathy (HCM), Brugada Syndrome, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), and Short QT Syndrome (SQTS). One of these syndromes, Brugada, is the most common cause of sudden death in young men without known underlying cardiac disease (implicated in 20% of cases) and thought to be responsible for up to 10% of deaths from sudden infant death syndrome. It is characterized by abnormal electrocardiogram (ECG) findings and an increased risk of sudden cardiac death. Because Brugada syndrome is a recently identified condition, the true incidence of Brugada is unknown but thought to be approximately 1 in 5000. Approximately 20% of the cases of Brugada syndrome have been shown to be associated with mutation(s) in the SCN5A gene that encodes for the sodium ion channel in the cell membranes of the muscle cells of the heart. The cause of death in Brugada syndrome is ventricular fibrillation. The episodes of syncope (fainting) and sudden death (aborted or not) are caused by fast polymorphic ventricular tachycardias or ventricular fibrillation. These arrhythmias appear with no warning and commonly occur during sleep, rest or fever. There is currently no known treatment. Exemplar Genetics has introduced a point mutation into the SCN5A gene in the genome of a pig to imitate Brugada syndrome and these pigs are currently available for investigational purposes.
The SCN5A pigs produced by Exemplar Genetics are discussed or studied in the following publications:
- Bringing home the bacon? The next step in cardiac sodium channelopathies
Arthur A.M. Wilde1,2 and Pieter G. Postema1
1Department of Cardiology, Heart Center, Academic Medical Center, Amsterdam, The Netherlands. 2Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia.
- Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias
David S. Park,1,2 Marina Cerrone,1 Gregory Morley,1 Carolina Vasquez,1 Steven Fowler,1,2 Nian Liu,1 Scott A. Bernstein,1,2
Fang-Yu Liu,1 Jie Zhang,1 Christopher S. Rogers,3 Silvia G. Priori,1,4 Larry A. Chinitz,1,2 and Glenn I. Fishman1 1Leon H. Charney Division of Cardiology and 2Heart Rhythm Center, New York University School of Medicine, New York, New York, USA. 3Exemplar Genetics, Coralville, Iowa, USA. 4Fondazione Maugeri IRCCS,
Department of Molecular Medicine, University of Pavia, Pavia, Italy.