Neuroscience research has long relied on the use of mouse models as a controllable way to study the brain, model human diseases and disorders, research behavior, and develop new therapies. And this research has historically and significantly favored male mice over female mice due to the belief that female mice’s hormonal cycles made their behavior less consistent. But new research out of Harvard Medical School suggests that this assumption may have been wrong. In fact, female mouse behavior may be more stable than that of their male counterparts. What does this mean for neuroscience research? Re-examining previous assumptions about animal models may have a positive impact on the quality of neuroscience research across the board, especially when it comes to outcomes for women.
History of the Mouse Model
Rodents have long been the most widely used animal model in biomedical research, with more of an emphasis on mouse models over the past two decades. Neuroscientific research, in particular, relies on mouse models to understand the etiology, pathophysiology, and pharmacology of a wide range of neuropsychiatric, neurocognitive, and neurodegenerative disorders and diseases.
Gender Bias in Research
Male mice have historically been strongly preferred over female mice of a model in research: a 2011 research analysis found five times more single-sex neuroscience studies utilizing male mice than female mice. There are several reasons for this disparity. As Sandeep Robert Datta, professor of neurobiology at the Blavatnik Institute at HMS and the new study’s co-author, explains, “Part of it is just plain old sexism, and part of it is conservatism in the sense that people have studied male mice for so long that they don’t want to make a change.”
Another purported reason for this bias has been a long-held concern about the effect that female mice’s fluctuating hormonal cycles would have on the stability of their behavior.
But new research from Harvard Medical School appears to indicate that these concerns have been largely unjustified.
Gendered Mouse Behavior Concerns Unfounded
A study conducted by Datta and Dana Levy, a research fellow in neurobiology at HMS, sought to measure the degree to which the estrous cycle in female mice influenced behavioral patterns of exploration.
“We assumed,” says Levy, “like everybody else, that adding females was just going to complicate our experiments.”
That assumption proved to be wrong. Not only did estrous status not affect the exploratory behavior of female mice, but female mice demonstrated more stable behavior than their male counterparts. In other words, female mouse behavior is more reliable, making them a better candidate for research than the male mice that have historically been used.
“People have been making this assumption that we can use male mice to reliably make comparisons within and across experiments, but our data suggest that female mice are more stable in terms of behavior despite the fact that they have the estrous cycle,” Datta explains.
Implications for the Future
The gendered bias in research has a real-world impact: focus on male over female mice of a mouse model means that the female brain is less understood. This research gap results in the misdiagnosis of mental and neurological conditions in women, inadequate treatment, increased medication side effects, and more. Beginning to shift from male mice to female mice could mean better outcomes and treatment options — not just for women, but for everyone.
Datta’s study only looked at one mouse strain in one particular lab setup, and further testing is needed to understand if these results will generalize. But the results were significant enough that Datta’s lab has already made the change from male mice to mixed or female-only groups. The researchers hope that these early findings will encourage drug developers to start using both sexes in their research and analysis.
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