Using CRISPR-Cas9 technology, scientists have managed to alter the social behavior of hamsters and make them far more aggressive, surprising the study authors. They had intended on reducing aggression by gene editing, but the results were exactly the opposite, suggesting biological mechanisms behind socialization and personality may be far more complex than previously thought, and genetic editing can have a direct impact on the way animals – and likely humans – could interact with others.
The study, published in the Proceedings of the National Academy of Sciences, was designed to test the ability of CRISPR-Cas9 at editing a major neurochemical signaling pathway and understanding any resulting social changes, using Syrian hamsters as a model organism. Vasopressin, and its receptor Avpr1a, were the targets for genetic editing, and have been implicated in a wide array of social skills, such as bonding, aggression, and even monogamy.
Using CRISPR-Cas9 editing, the researchers from Georgia State University created hamsters without Avpr1a receptors, entirely blocking vasopressin activity, before running multiple tests on them to determine the gene editing was successful. The hamsters were then mixed with littermates and compared to wild-type (non-edited hamsters) to understand their aggression levels and social behavior.
As vasopressin is linked to aggression, the researchers hypothesized that decreasing the activity of vasopressin by stopping the activity of the receptor it binds to would reduce aggression.
However, the results didn’t match their expectations at all.
“We were really surprised at the results,” said senior author Elliott Albers in a statement. “We anticipated that if we eliminated vasopressin activity, we would reduce both aggression and social communication. But the opposite happened.”
Instead, the hamsters began communicating much more between littermates and became more aggressive alongside. This aggressiveness did not follow the typical pattern in which males are more aggressive than females – both males and females became aggressive towards other same-sex hamsters. The findings suggest we need to start thinking on a wider scale when considering genetic editing, even when the expected effects are thought to be relatively small.
“We don’t understand this system as well as we thought we did. The counterintuitive findings tell us we need to start thinking about the actions of these receptors across entire circuits of the brain and not just in specific brain regions,” continued Albers.
The researchers now wish to use their new understanding of vasopressin, and how Avpr1a seemingly leads to inhibition of aggression compared to increasing it, to combat a wide array of psychiatric conditions that may be related. Meanwhile, CRISPR-Cas9 researchers need to be extremely careful in how they approach neurological genetic editing.
“Developing gene-edited hamsters was not easy,” Albers said.
“But it is important to understand the neurocircuitry involved in human social behavior and our model has translational relevance for human health. Understanding the role of vasopressin in behavior is necessary to help identify potential new and more effective treatment strategies for a diverse group of neuropsychiatric disorders ranging from autism to depression.”