Mice bred to produce too much of a protein associated with a particular form of calcium channel gene experience a "pure" form of absence seizures, identified by brief lapses in consciousness, said researchers at Baylor College of Medicine in a report that appears in the current issue of the Journal of Neuroscience.
"This shows that an extra copy of a gene in a mouse can cause a pure form of absence epilepsy, without any other neurological problems" said Dr. Jeffrey L. Noebels, professor of neurology, neuroscience and molecular and human genetics. He is director of the Blue Bird Circle Developmental Neurogenetics Laboratory, where this research took place. Noebels said much of the work was done by Dr. Wayne Ernst while a graduate student in his laboratory.
The model is already proving useful in screening drugs that work against calcium channel defects, he said.
Calcium channels are special pores in cell membranes that open and close to let in charged calcium molecules at appropriate times in the life of a cell. Too much or too little calcium can affect the cell’s ability to carry out its normal function. Such defects in neurons are associated with epilepsy and other neurological disorders.
Childhood absence epilepsy accounts for 2 to 8 percent of all epilepsy in children. Most such seizures are spells in which the child is not aware of his or her surroundings and is not responsive. Such spells last only seconds, in most cases.
Previous studies had produced mice that had absence epilepsy as well as ataxia, a disorder associated with problems walking and standing.
When the new "T-type" calcium channel gene is overexpressed in the neurons by inserting a second copy of the gene, it causes the pure form of absence epilepsy similar to that seen in children. In a twist of the old song, the mouse now has "two for T", said Noebels.
Funding for this research came from the National Institute of Neurological Disorders and Stroke, the National Institute of Child Health and Human Development and the Blue Bird Circle Foundation.
Others who took part in this research include Yi Zhang, Jong W. Yoo and Sara J. Ernst, all of BCM.