By studying the molecules that regulate the formation of muscle, researchers at UT Southwestern Medical Center have discovered a gene that may play a role in a rare muscular disease in humans.
While the researchers studied mice, they are now looking for patients who have mutations in this newly discovered muscle gene, Srpk3. Mice that lack the gene have a condition much like the human disease, centronuclear myopathy.
"It's easy to imagine that human patients could have symptoms similar to those we saw in mice," said Dr. Osamu Nakagawa, assistant professor of internal medicine and the paper's lead author. "The human research is just starting, but already we found patients who may have mutations in the gene."
The researchers' work appears in the Sept.1 issue of Genes and Development.
There are several forms of centronuclear myopathy, including one that is apparent at birth. Children with the condition have trouble moving or breathing and often must depend on ventilators. Other forms show up later in life.
"Treatment may be in the far distant future, but I think diagnosis is very important," Dr. Nakagawa said. Knowing the form of the condition could guide treatment, for instance.
Dr. Eric Olson, senior author and chairman of molecular biology, said, "The discovery of this new muscle gene is very exciting because it sheds light on a biochemical process involved in the muscle-wasting disorder centronuclear myopathy. This information represents a first step toward potential therapies to improve muscle function during disease." Dr. Olson directs the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and the Nearburg Family Center for Basic Research in Pediatric Oncology.
The first stage of the UT Southwestern study involved searching for important muscle genes downstream of muscle-specific gene regulation. Scientists have known that one protein, called MEF2, is essential to the formation of skeletal muscles and heart, but didn't know its exact mechanism.
The researchers found that one of MEF2's jobs is to activate the gene they discovered, Srpk3. Dr. Nakagawa compared Srpk3 to a light bulb and MEF2 to the switch: MEF2 binds to DNA, and that action turns on the gene that creates the Srpk3 protein.
You need both genes for normal function, he said. "If you have a switch but no light bulb, the room would remain dark."