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Of Mice, Rabbits, And Men: New Rabbit Model Of Sudden Cardiac Death Provides Insight Into The Human Disease

Date:
May 11, 2008
Source:
Journal of Clinical Investigation
Summary:
Individuals with long QT syndrome are at increased risk of sudden death due to irregular heartbeats (also known as a cardiac arrhythmias). Although mutations in several genes have been shown to cause the disease, the most commonly affected genes are KCNQ1 and KCNH2.

Individuals with long QT syndrome (LQTS) are at increased risk of sudden death due to irregular heartbeats (also known as a cardiac arrhythmias). Although mutations in several genes have been shown to cause the disease, the most commonly affected genes are KCNQ1 and KCNH2.

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New insight into the mechanisms by which these mutations might produce an irregular heartbeat in humans has been provided by Gideon Koren and colleagues, at Brown University, Providence, who have generated two rabbit models of LQTS.

Although mouse models of LQTS have enhanced our understanding of many aspects of the disease, there are important differences between mice and humans that limit the applicability of some studies to individuals with LQTS.

Many of these differences are not found in rabbits, the authors therefore generated rabbits expressing either KCNQ1 or KCNH2 mutants that generate proteins with the same functional defect as found in individuals with LQTS. The heart defects observed in the rabbits mirrored those observed in individuals with LQTS and more than 50% of the rabbits carrying the KCNH2 mutant died suddenly due to irregular heartbeats in their first year of life.

The proteins generated by the KCNQ1 and KCNH2 mutants prevented proteins generated by the corresponding nonmutant form of the gene from working and, importantly, no compensation for the loss of function of either protein was observed. As compensation for the loss of function of the proteins generated by the KCNQ1 and KCNH2 mutants is observed in mouse models of LQTS these data provide important insight into the mechanisms underlying the disease.


Story Source:

The above story is based on materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal Reference:

  1. Mechanisms of cardiac arrhythmias and sudden death in transgenic rabbits with long QT syndrome. Journal Of Clinical Investigation. May 8, 2008.

Cite This Page:

Journal of Clinical Investigation. "Of Mice, Rabbits, And Men: New Rabbit Model Of Sudden Cardiac Death Provides Insight Into The Human Disease." ScienceDaily. ScienceDaily, 11 May 2008. <www.sciencedaily.com/releases/2008/05/080508174839.htm>.
Journal of Clinical Investigation. (2008, May 11). Of Mice, Rabbits, And Men: New Rabbit Model Of Sudden Cardiac Death Provides Insight Into The Human Disease. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2008/05/080508174839.htm
Journal of Clinical Investigation. "Of Mice, Rabbits, And Men: New Rabbit Model Of Sudden Cardiac Death Provides Insight Into The Human Disease." ScienceDaily. www.sciencedaily.com/releases/2008/05/080508174839.htm (accessed October 24, 2014).

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