Introduction
Mice constantly appear on the headlines of news articles next to a new finding in biomedical research. Laboratory mice have allowed researchers to study cancer, genetic conditions, and all sorts of diseases. But why mice? Why is it that mice are so involved in medical research? What do these creatures that seemingly bear little connection with humans offer to researchers?
The beginning of mouse genetics research started in 1902 when Lucien Cuénot experimented with coat colors of mice to show that Mendel’s laws of inheritance–which were proved using sweet peas–also applied to mammals. Mice were seen as a more ideal research animal after Clarence Little created the first fully inbred strain of mice, DBA. This provided for genetically identical laboratory mice for experimental use (“How did the lab mouse come to be?”). The mouse genome was sequenced in 2002, and allowed for more research into the connection between mouse and human genes as well as health and diseases (“2002: Mouse Genome Sequenced”). Today, the most common species of laboratory mice is the House Mouse or Mus musculus.
Why Mice?
Mice serve as ideal animal models for genetics and biomedical research for a number of reasons. For one, they share similarities with humans in DNA. The protein-coding regions of mice and human DNA, which are important for function, are 85% identical. These genes are evolutionarily conserved and range from 60% identical to 99% identical (Parente).
Additionally, the bodies of mice and humans undergo similar processes and react similarly to diseases. Since the genes that mice and humans share have similar functions, mice have the same organs namely, the heart, brain, lungs, and kidneys. It also translates to similar bodily systems such as the circulatory, reproductive, digestive, hormonal, or nervous systems (“Why are mice considered excellent models for humans?”). As such mice are susceptible to a number of the same diseases as humans. For instance, they naturally develop conditions such as diabetes, cancer, and high blood pressure and when linked to genetics, the DNA that mice and humans share provides opportunities to study those genetically-linked conditions. Although they are not perfect, these parallels allow researchers to gain insight into the development of both humans and diseases.
Lastly, mice are convenient animal models for researchers. They reproduce quickly, sometimes reproducing after nine weeks. Mice are small mammals, and they produce larger numbers of offspring. These factors make them economical to maintain and study. In addition, every one mouse year is the equivalent of 30 human years; this means that the entire life cycle of humans can be replicated in a few mouse years, allowing researchers to study aging and diseases over time (Parente).
The mouse genome can also be easily edited to study a specific gene or disease. Knockout or knock-in mice have been used to study the role of specific genes through gene manipulation. By using a process in DNA repair called homologous recombination, artificial pieces of DNA can be introduced into the cell nucleus of mouse embryonic stem cells (cells from young mouse embryos). The cells with the manipulated piece of DNA are then injected into a surrogate female mouse. This process allows a targeted gene to be neutralized, as the artificial piece of DNA replaces or “knocks out” the original. Genes or mutant genes can also be introduced to produce knock-in mice that have a desired gene (Parente). Researchers use these mice to study the effects of the loss of a specific gene or the introduction of a mutant gene. This also allows researchers to introduce genes that would make mice susceptible to a specific condition, creating opportunities to study a specific disease.
Xenografting is another type of mouse model in which immunodeficient mice (mice with defective immune systems) are transplanted with cells from another species. Human cancer cells or tumor tissues are often transplanted. This allows for the studying of the effect of an anticancer drug on the mice and tumors (Parente). Transgenic mice, on the other hand, are inserted with genes from another source, specifically humans; this allows for a human gene that does not naturally occur in mice to be expressed in mice. For instance, when the human growth hormone gene was inserted using this technique, it resulted in large mice. Transgenic research has resulted in a better understanding of genetic regulation and a number of other diseases (Parente).
Ethical Concerns
The role of mice in biomedical research raises ethical concerns over animal health and welfare. Lab mice should be housed in see-through plastic cages with bedding and fed a specific nutritional diet. It is also important to provide them with enrichment and to house them with other mice in groups or pairs, as they are social animals (“Mouse”). There are existing guidelines and policies regarding animal experimentation; most provide strict regulation of laboratory animals. One widely used principle is that of the 3Rs (Replacement, Reduction, and Refinement), which aims to provide a framework for more humane animal studies. When possible, technologies or approaches that can fully or partially replace animals in experiments should be used. The number of animals used per experiment should be minimised while still allowing for the study to be conducted. Lastly, methods that minimise the pain, suffering, distress, or harm of a research animal should be taken to avoid compromising the results (“The 3Rs”). Laboratory mice in biomedical research are stand-ins for humans when studying diseases. It is important that their welfare is ensured, as they play an important role in furthering scientific knowledge.
Conclusion
Mice may not seem like ideal test subjects in research studies, but they bear a surprising resemblance to humans in their physiology and DNA. In this way, mice provide researchers with a convenient window into human genetics and diseases. Despite the ethical concerns of animal experimentation, it is undeniable that mice play a central role in biomedical research that is vital to furthering our understanding of human health.
Michelle Li, Youth Medical Journal 2021
References
“The 3Rs.” National Center for the Replacement Reduction and Refinement of Animals in Research, nc3rs.org.uk/the-3rs. Accessed 31 Jan. 2021.
“How did the lab mouse come to be?” The Jackson Laboratory, http://www.jax.org/why-the-mouse/lab-mouse. Accessed 31 Jan. 2021.
“Mouse.” Understanding Animal Research, http://www.understandinganimalresearch.org.uk/animals/a-z-animals/mouse/. Accessed 31 Jan. 2021.
Parente, Matilde. “Mouse Model.” Genetics, 2nd ed., vol. 3, Gale, 2018, pp. 127-32. Gale in Context: Science, link.gale.com/apps/doc/CX2491300180/SCIC?u=mlin_m_newtnsh&sid=SCIC&xid=e28e17be. Accessed 31 Jan. 2021.
“2002: Mouse Genome Sequenced.” National Human Genome Research Institute, http://www.genome.gov/25520486/online-education-kit-2002-mouse-genome-sequenced. Accessed 31 Jan. 2021.”Why are mice considered excellent models for humans?” The Jackson Laboratory, http://www.jax.org/why-the-mouse/excellent-models. Accessed 31 Jan. 2021.
Youth Medical Journal 