Princeton molecular biology and neuroscience researchers published findings revealing that the Agouti gene, which is found in humans as well as mice, can serve as an on-off switch for paternal aggression in African striped mice. The research was published in Nature magazine on Wednesday.
The Agouti gene, a gene that codes for proteins in the medial preoptic part of the brain, is negatively associated with caring behavior in African striped male mice. This means that high levels of Agouti lead to more aggressive behavior from mice fathers to their pups, sometimes even resulting in infanticide.
Co-authors of the paper, including Postdoctoral Research Fellow Forrest Rogers, Princeton Neuroscience Institute Assistant Professor Catherine Peña, Associate Professor of Molecular Biology Ricardo Mallarino, Taso Callanan ’26, and Sarah Kim ’26, spoke with The Daily Princetonian to discuss their findings.
Rogers said in an email to the ‘Prince’ that the research was inspired by field observations in which they were investigating parental patterns in mice. After running further behavioral experiments and RNA-sequencing analysis, the researchers found that Agouti made male mice less prone to care for their young.
Mallarino initially worked with African striped mice as part of his research on understanding the evolution of certain traits across species, he described to the ‘Prince.’ He sought out Peña to better grasp the brain regions that were controlling paternal behavior in the mice. Peña then brought on Rogers, who has been studying paternal care in species since 2011, his first year as an undergraduate.
“I think there were a lot of surprises throughout the study,” Rogers said in an interview with the ‘Prince.’ “[Agouti] is a gene that’s not very well-characterized in the brain at all and not previously characterized in playing a role in parental care.”
Mallarino noted that the Agouti gene has previously most been studied for its role in skin pigmentation.
Their research suggests that the environment can affect the expression of the gene. Male mice who spent more time in crowded, social environments had a higher expression of Agouti while those who were more socially isolated had a lower expression of it.
“I think one of the really cool things about this study is that we found a single molecule that actually responds to environmental conditions and the social environment and takes those cues, whatever those cues are, into the brain, and is able to fine-tune behavior and parenting behavior based on those social cues,” Peña said.
“We’re highlighting that animals are flexible in their behavior and adapt to their environmental circumstances, which is very different from the way that a lot of people talk about their parenting, because people often talk about parenting as something that’s automatic without much adjustment for environmental circumstances,” Rogers said.
Both undergraduate co-authors of the research paper, Kim and Callanan, are using these results as a foundation for their senior theses.
Kim’s project tackles the question of timeline. While the researchers found that the level of gene expression varied as a result of the environment, they are still researching the specifics of the integration process of the gene. Rogers is working with Kim on determining what cue in the social environment is triggering the animals to change their behavior and how Agouti develops.
“My thesis project is, [at] what stage of the developmental process do we see a spike [of Agouti], if we see a spike?” Kim said in an interview with the ‘Prince.’ “Or, what’s the trajectory [of the gene] while [the mice] grow up during social isolation?”
There are still matters unknown about how Agouti functions outside the medial preoptic area of the brain. Callanan is focused on understanding how the gene works in an entire neural circuit, not just in one specific region of the brain.
“My thesis is more so looking at the molecular basis of Agouti and how it’s expressed brain-wide,” Callanan said.
Ultimately, Rogers noted that “this work hasn’t been replicated in other species yet, so we won't say whether or not the same exact mechanisms apply to other mammals or humans.”
However, Rogers emphasized: “we do think that there has to be some other mechanism, if not the same mechanism…that allows other animals to take in information about their environments and adjust their behavior.”
The full research paper can be found here.
Danielle Burke is a News contributor for the ‘Prince.’ She is from New Jersey and can be reached at db5008[at]princeton.edu.
Please send any corrections to corrections[at]dailyprincetonian.com.
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