New epilepsy gene identifi...( Researchers have identified a novel ge...)

Researchers have identified a novel gene that is mutated in mice that develop spontaneous epileptic seizures in response to loud noises. The brain protein affected by the mutation is unlike any other known to cause epilepsy in mice or humans.

In an article published in the August 30, 2001, issue of the journal Neuron, a research team led by Howard Hughes Medical Institute investigator Louis J. Ptacek at the University of Utah reported cloning and sequencing the gene that is responsible for an audiogenic form of reflex epilepsy in the Frings mouse strain. Although this mouse strain -- in which seizures can be triggered by a loud noise -- has been used in research for half a century, the genetic defect underlying the disorder had been unknown.

"The Frings mouse shows a form of audiogenic reflex epilepsy precipitated by sound. This is a common form of epilepsy in mice and is similar to the human reflex epilepsies triggered by stimuli such as strobe lights," said Ptacek. "Since the same antiepileptic drugs that work in other forms of epilepsy also work in this form, we are hoping that this will be a generalizable and useful model of epilepsy."

In earlier work, Ptacek and his colleagues narrowed the search for the Frings defect to a region of DNA, or locus, on mouse chromosome 13. Compared to other mouse models of audiogenic epilepsy, where mutations were thought to reside at multiple loci, the Frings mice appeared to be unusual because their mutation was in a single locus.

After narrowing their search, Ptacek and his colleagues then set out to map this locus finely enough to identify the specific causative gene. "It was just a matter of brute force, in which we generated a colony of twelve hundred mice and performed genotyping on them to home in on the gene," said Ptacek.

"Eventually, we localized the gene to precisely thirty six thousand base pairs and just sequenced that whole region." DNA sequencing showed that only one ge
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
29-Aug-2001