A semi-natural habitat to enhance research mouse models

In the environment created by Sébastien Hébert and his team, laboratory mice wer
In the environment created by Sébastien Hébert and his team, laboratory mice were able to demonstrate many natural behaviors, such as digging tunnels, climbing, running and hiding food. - Courtesy

Study shows that a more diverse environment modifies their immune systems and lungs, offering a complementary solution for biomedical research

Recreating more natural living conditions for laboratory mice is the goal of Sébastien Hébert, professor in the Faculty of Medicine and affiliated researcher at the Centre de recherche du CHU de Québec - Université Laval. With his team, he has developed a semi-natural environment to study how this complex environment influences animal health. Initial studies, notably on the immune system and lungs, suggest that this type of habitat could offer a complementary model to the approaches used in biomedical research.

Professor Hébert points out that mice traditionally studied in the laboratory live in highly sanitized environments. The aim, he warns, is not to replace these traditional models, which remain essential for many biomedical questions. But since mice are much less exposed to microbes than a human in everyday life, their immune systems don’t develop in the same way. The research team wondered whether adding diversity to their environment might help to better understand some of the differences observed between mice and humans, particularly in the way they respond to various treatments.

Rethinking the laboratory mouse environment

To answer this question, his team recreated a semi-natural laboratory environment using a large canvas pool filled with garden soil, peat, plants and hay, with the natural microorganisms found there. "We wanted to bring the outdoors indoors, while maintaining strictly safe and controlled conditions, for temperature or light levels for example," explains Sébastien Hébert.

Once settled in this more diversified environment, the mice quickly made the space their own. They displayed many natural behaviors. "They made little tunnels, they climbed, they ran, they hid food", reports Professor Hébert.

By incorporating key elements of the mice’s natural habitat, the scientists wanted to stimulate the maturation of their immune system, a process that takes around three months, and document the effect on their overall health. "The immune system affects the whole body," says PhD student Mohamed Lala Bouali, first author of the study. Having models that reproduce different living conditions therefore makes it possible to explore various human-related aspects. Mice raised in sanitized environments are also much more sedentary, he adds, a factor known to affect health in both humans and animals.

Promising models for studying disease

The research team focused on the effects of the semi-natural environment on the lung, in collaboration with the Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval. The results show significant differences compared to mice raised in a sanitized environment, which could influence asthma research in particular, says Mohamed Lala Bouali. The researcher explains that a substance normally associated with asthma, in both humans and mice raised in aseptic environments, appeared to help mice housed in semi-natural environments and exposed to the microorganisms of this environment to breathe more easily. In his view, this surprising result may be due to the fact that these mice have a more stable immune system. Instead of going into overdrive and triggering severe inflammation, it adjusts its response to maintain a better balance.

The semi-natural habitat could therefore offer a complementary model for studying diseases involving the immune system, such as multiple sclerosis or pneumonia. The laboratory is also working on a model of Alzheimer’s disease using these mouse models to assess how the environment might affect the brain.

According to Prof. Hébert, the semi-natural environment approach offers an additional modular tool that can be adapted to simulate various environments, such as pollution. The habitat under study is currently quite large, but his team is working on a more compact semi-natural environment. "We’re adding some of the complexity we see in humans. In other words, we’re bringing the animal model closer to the real world," he sums up.

Signatories of the study, published in the journal Mucosal Immunology, Mohamed Lala Bouali, Amir Mohamed Kezai, Marie-Josée Beaulieu, Joanny Roy, Papa Yaya Badiane, Véronique Lévesque, Luc Filion, Luc Vallières, Marie-Renée Blanchet and Sébastien Hébert.