Scientists at Georgetown University Medical Center, the National Institutes of Health and Childrens National Medical Center have created genetically altered mice with symptoms resembling those of human patients with Jervell and Lange-Nielsen Syndromea rare disorder characterized by deafness from birth and cardiac abnormalities that can cause potentially fatal arrhythmias. These findings will be published in the February 27 issue of Proceedings of the National Academy of Sciences (PNAS).

Having the animal model will enable scientists to study the underlying mechanisms of Jervell and Lange-Nielsen Syndrome, and ultimately come up with new strategies for alleviating the problems it causes, said Steven Ebert, PhD, assistant professor in Georgetowns Department of Pharmacology. Until now we have had only a vague understanding of how arrhythmias are precipitated. This new model should enable us to study the mechanisms responsible for triggering potentially lethal cardiac arrhythmias.

NIH researchers led by Karl Pfeifer, PhD, created the mice with the genetic defect mimicking the human disease, while the Georgetown researcherswho in addition to Ebert included Bjoern Knollmann, MD, PhD, Assistant Professor of Clinical Pharmacology and Michael Franz, MD, PhD, Professor of Pharmacologystudied the cardiac abnormalities.

They found that by removing a specific protein known as KCNQ1 from laboratory mice, they were able to recreate the bilateral deafness, difficulties with balance and movement, and abnormal electrocardiogram patterns typical of Jervell and Lange-Nielsen Syndrome. These results indicate that KCNQ1 is required for both normal inner ear and cardiac function.

Jervell and Lange-Nielsen Syndrome is a relatively rare, inherited form of a more broadly defined disorder called Long QT Syndrome, which is also associated with increased risk of developing potentially lethal cardiac arrhythmias, and can be either inherited or acquired through disease or dr
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Contact: Beth Porter
bap2@georgetown.edu
202-687-4699
Georgetown University Medical Center
25-Feb-2001