What Novel Rodent Models Can Teach Us About Women’s Health
Author: Julia Mazur, MSc Student, Cell and Systems Biology, University of Toronto Mississauga | Editors: Tashi Stampp, Romina Garcia de leon (Blog Coordinators) | Reviewer: Jesse Lacasse
Rodent models are an essential aspect of pre-clinical research because they allow scientists to investigate underlying causes of health and disease in a living organism. Although rodents appear different in many ways, they share many biological features with us, making them very useful in translational research. They can also be designed to exhibit certain characteristics of human diseases, which allows for investigation into how diseases develop and progress at a mechanistic level.
Rodents are also practical to study, given their small size, fast rate of reproduction, and they are relatively easy to care for. Mice and rats are the most commonly used animals in preclinical research, as they are well-characterized and have provided invaluable information in many fields of research. Without mice and rats, many of the treatments that are used today would not exist.
But what about other rodent models?
Mice and rats alone do not capture the full diversity of human health and disease. For this reason, investigating other species can offer insight into other diverse biological traits. By including work in other species, we may be able to unlock answers as to how and why we evolved the way we did. For example, we may be able to find features in other models that allow for more robust study of molecular pathways.
Naked Mole Rats
Despite the critical contributions of mice and rats to biomedical research, there are some limitations to these traditional models that may be addressed by using novel models, such as studying factors associated with lifespan and aging. For instance, the naked mole-rat is a rodent that can live longer than 35 years and is highly resilient to the development of cancers, metabolic disorders, and neurodegenerative diseases. This provides a distinct advantage as they permit long-term studies that better resemble human lifespan, while maintaining practicality given their small size and quick reproductive rate. Scientists can examine these unique properties to figure out what makes these animals “aging-resistant”, which could lead to the development of therapies in several human age-related diseases.
Naked mole-rats also offer insight to health in early-life, specifically in puberty and reproductive onset. They naturally exhibit extreme reproductive suppression, such that in their colonies, there is only one breeding queen and usually one breeding male. The remainder of the colony members remain pubertally-suppressed, with a greater effect in females. When removed from their colonies, naked mole-rats will go through puberty at any age. This unique trait allows researchers to investigate the mechanism that “turns puberty on” and how external factors, like stress and environment, may play a role in this switch. The greater suppression of reproductive capacity in female naked mole-rats can be used to investigate the underlying differences in male and female responses to stressors and environment, with respect to puberty onset. For instance, beginning around the time of puberty and continuing into adulthood, women are twice as likely to be affected by depression and anxiety compared to men. This model allows us to control when and under what environment, puberty is initiated thus allowing for the investigation of sex specific factors that result in this increased risk in females.
Degus
Another example of a less common model with great advantages are degus. One primary advantage of these rodents is that they can spontaneously develop amyloid-beta plaque deposits and tau neuropathology, two major components of Alzheimer’s disease. This is atypical of rodents as most rodent models must be genetically engineered to produce these disease characteristics. Degus may potentially provide a new model in the continuous fight against Alzheimer’s disease, as they can naturally develop similar pathology and do not require genetic engineering. Aged female degus are reported to display altered brain signalling in the hippocampus, a primary brain region impacted by Alzheimer’s disease, when compared to aged male degus. This finding is important and translates to the human condition, as women comprise two-thirds of all Alzheimer’s disease cases. Additionally, degus with diabetes often experience progression of symptoms similar to those in humans, where they will exhibit impaired management of glucose followed by cataract development and blindness. Their high susceptibility to human-like pathologies demonstrates promise in using them to tease apart the molecular interactions in these diseases and ultimately apply this information to advance therapeutic development.
A new approach to translational work
When selecting an animal model, it is imperative that researchers pause to think about what the model can provide to answer the overarching question. A question to consider may be: “Does this model adequately encompass as many aspects of human health or disease as it possibly can?”. It is crucial to remember that no scientist will ever be able to choose a model that is all-encompassing and covers every aspect of human health and disease. For this reason, most rodent models will focus on modelling “aspects” of the disease. However, rodents like naked mole rats, and degus may be able to provide more comprehensive translatability to humans. There will always be limitations to any model, whether it be traditional or novel. By recognizing that and choosing the best possible model for the study, the highest quality of patient-focused preclinical research can be achieved.
