Doh! Emory researchers discover the ‘Homer Simpson’ gene

By Quinn Eastman

Lab mouse sniffing frosted doughnut with sprinkles

Deleting a specific gene in mice can make them smarter by unlocking a mysterious region of the brain considered to be relatively inflexible, scientists at the School of Medicine have found.

Mice with a disabled RGS14 gene are able to remember objects they have encountered and learn to navigate mazes better than regular mice, suggesting that the gene’s presence limits some forms of learning and memory.

Since RGS14 appears to hold mice back mentally, Professor of Pharmacology John Hepler says he and his colleagues have jokingly called it the “Homer Simpson gene.”

RGS14, which is also found in humans, was identified more than a decade ago, and is primarily active in one particular part of the hippocampus—a region of the brain involved in consolidating new learning and forming memories.

Without it, the ability of the gene-altered mice to recognize objects previously placed in their cages was enhanced, compared to normal mice. They also learned more quickly to navigate through a water maze to a hidden escape platform by remembering visual cues.

“A big question this research raises is why would we, or mice, have a gene that makes us less smart—a Homer Simpson gene?” Hepler says. “I believe that we are not really seeing the full picture. RGS14 may be a key control gene in a part of the brain that, when missing or disabled, knocks brain signals important for learning and memory out of balance.”

The lack of RGS14 doesn’t seem to hurt the altered mice, but it is possible that they have had their brain functions changed in a way that researchers have yet to spot.

“The pipe dream is that maybe you could find a compound that inhibits RGS14 or shuts it down,” Hepler says. “Then, perhaps, you could enhance cognition.”

The research was supported by the National Institutes of Health.

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