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Assessing Social Dominance in Mouse Models Using the Tube Test
Published on: June 6, 2025
Absence of M-Ras modulates social behavior in mice
Annette Ehrhardt1, Bin Wang2, Marie J Leung3
1The Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, V6T 1Z3, Canada. annette@brc.ubc.ca.
Background:
The molecular mechanisms that determine social behavior are poorly understood. Pheromones play a critical role in social recognition in most animals, including mice, but how these are converted into behavioral responses is largely unknown. Here, we report that the absence of the small GTPase M-Ras affects social behavior in mice.
Results:
In their interactions with other males, Mras(-/-) males exhibited high levels of territorial aggression and social investigations, and increased fear-related behavior. They also showed increased mating behavior with females. Curiously, increased aggression and mating behaviors were only observed when Mras(-/-) males were paired with Mras(-/-) partners, but were significantly reduced when paired with wild-type (WT) mice. Since mice use pheromonal cues to identify other individuals, we explored the possibility that pheromone detection may be altered in Mras(-/-) mice. Unlike WT mice, Mras(-/-) did not show a preference for exploring unfamiliar urinary pheromones or unfamiliar isogenic mice. Although this could indicate that vomeronasal function and/or olfactory learning may be compromised in Mras(-/-) mice, these observations were not fully consistent with the differential behavioral responses to WT and Mras(-/-) interaction partners by Mras(-/-) males. In addition, induction of c-fos upon pheromone exposure or in response to mating was similar in WT and Mras (-/-) mice, as was the ex vivo expansion of neural progenitors with EGF. This indicated that acute pheromone detection and processing was likely intact. However, urinary metabolite profiles differed between Mras(-/-) and WT males.
Conclusions:
The changes in behaviors displayed by Mras(-/-) mice are likely due to a complex combination of factors that may include an inherent predisposition to increased aggression and sexual behavior, and the production of distinct pheromones that could override the preference for unfamiliar social odors. Olfactory and/or social learning processes may thus be compromised in Mras(-/-) mice.
Insights
Mice lacking M-Ras exhibit altered social behaviors, including increased aggression and mating. These changes may stem from modified pheromones and compromised social learning, impacting how they recognize and interact with others.
Area of Science:
- Neuroscience
- Behavioral Genetics
- Animal Behavior
Background:
- Social behavior mechanisms are poorly understood.
- Pheromones are crucial for social recognition in animals like mice.
- The role of small GTPase M-Ras in social behavior is largely unknown.
Purpose of the Study:
- Investigate the impact of M-Ras absence on mouse social behavior.
- Determine how M-Ras deficiency affects social recognition and interaction.
- Explore potential alterations in pheromone detection and processing.
Main Methods:
- Behavioral assays comparing M-Ras knockout (Mras(-/-)) and wild-type (WT) mice.
- Analysis of social investigation, aggression, and mating behaviors.
- Assessment of pheromone preference, olfactory learning, and neural responses (c-fos induction).
- Urinary metabolite profiling.
Main Results:
- Mras(-/-) males displayed increased aggression, social investigation, and mating behavior, particularly with Mras(-/-) partners.
- Preference for unfamiliar pheromones and mice was reduced in Mras(-/-) mice.
- Acute pheromone detection and neural processing appeared intact, but urinary metabolite profiles differed.
- Behavioral responses varied significantly depending on the interaction partner's genotype.
Conclusions:
- Altered social behaviors in Mras(-/-) mice result from a combination of factors.
- Increased aggression and sexual behavior may be inherent.
- Distinct pheromones produced by Mras(-/-) mice might override normal social odor preferences.
- Olfactory and/or social learning processes may be compromised in M-Ras deficient mice.

