Modifier Gene Active in Neurologic Disease Model

Researchers have found that the severity of certain types of inherited neurologic disorders is influenced by a specific modifier gene that interacts with other genes to modulate the physical effects of the disease.

Investigators at the University of Michigan (Ann Arbor, USA) used C57BL/6J mice to study the sodium channel genes whose products control the flow of electrical signals between nerve and muscle cells. Mutations in sodium channel genes produce a variety of neurologic disorders including several types of epilepsy, ataxia, poor muscle coordination, paralysis, and cardiac arrhythmias. C57BL/6J mice possess a mutation in the Scn8a sodium channel gene.

"In our study with mice, we found that the severity of neurological defects caused by mutations in a gene called Scn8a are determined by another gene, Scnm1, which is located on a different chromosome,” explained senior author Dr. Miriam Meisler, professor of human genetics in the University of Michigan Medical School. "Scnm1 is expressed in many human cells, which suggests that it could modify the severity of a wide range of inherited disorders in humans, including other neurological diseases.”

The authors reported in a paper published in the August 15, 2003, issue of Science that the presence of the mutation caused the mice to produce an inadequate amount of critical sodium channel proteins. Mice with two copies of the mutated modifier gene had only 5% of the normal amount of functional Scn8a protein and died soon after birth.

"Now that we have identified the gene and the mechanism by which it works, as well as the precise chromosome location of the human gene, we can begin looking for interactions with other mutations associated with human neurological disorders like epilepsy,” said Dr. Meisler. "This modifier is likely to interact with other types of genes, in addition to human sodium channels. If we can find a way to change the secondary effects of modifier genes, we may be able to minimize the impact of the original genetic defect.”