When scientists aim to understand human health, they often turn to murine models. These are laboratory mice or rats used to study biological processes and diseases in a way that informs human medicine. The house mouse, or Mus musculus, is the most used species, serving as a living system where researchers can investigate complex health issues, from genetic disorders to infections.
The use of these models allows for the examination of questions that would be impossible to explore directly in humans. By observing these animals, scientists gain insights into how diseases develop, progress, and respond to potential treatments. This foundational work is a widespread practice in biomedical research, with mice and rats making up the vast majority of animals used in laboratories.
Why Mice and Rats Are Used in Research
The choice of mice and rats for research is based on biological similarities to humans and practical advantages. A primary reason is the genetic and physiological overlap. Mice share a high percentage of their genes with people, and their organ systems function in much the same way as ours. This shared biology means they can develop many of the same diseases, providing a relevant system for study.
Beyond biological parallels, these rodents have characteristics well-suited for laboratory settings. Their small size makes them easier and more cost-effective to house and care for than larger animals, which allows for larger-scale studies. The long history of using these animals also means there is a vast body of knowledge about their biology, making experimental outcomes more predictable.
Their short lifespan and rapid reproductive cycle are also valuable. Mice have a gestation period of about three weeks and live for two to three years. This compressed life cycle enables scientists to study developmental processes, aging, and diseases that unfold over many years in humans in a much shorter timeframe. It also allows for multigenerational studies to understand how traits or diseases are inherited.
Types of Murine Models
Researchers have developed various murine models to answer different scientific questions, categorized based on their genetic makeup. One fundamental category is the inbred strain. These are populations of mice bred for at least 20 generations of sibling or parent-to-offspring mating. This process results in animals that are genetically identical, which minimizes the chance that natural gene variations will influence an experiment’s outcome.
In contrast, outbred stocks are bred to maintain genetic diversity, which more closely mimics the genetic landscape of the human population. Such models are useful in fields like toxicology, where understanding how a diverse population responds to a substance is important.
A significant advancement is the creation of genetically engineered models, where the mouse’s DNA has been deliberately altered. A transgenic model has a foreign gene added to its genome, while a knockout model has had an existing gene inactivated. These techniques allow scientists to study the specific function of a single gene. Humanized mice are another type, where human genes, cells, or tissues are introduced to study human-specific diseases or test drugs.
Finally, some models are created by inducing a specific condition. Rather than altering genes, scientists might use external factors like a specific diet, a surgical procedure, or exposure to a substance to replicate a human health issue. For example, a high-fat diet can be used to study the mechanisms of obesity and its related complications.
Applications in Medical Research
Murine models are applied across a vast spectrum of medical research, contributing to the treatment of numerous human diseases. In oncology, they are used to study how tumors grow and spread and to test the effectiveness of new cancer-fighting drugs before human trials. Models with compromised immune systems are useful for this, as they can host human tumor grafts, allowing direct observation of a human cancer’s response to therapy.
The study of neurological disorders has also been advanced by these models. Researchers have developed mice that exhibit features of diseases like Alzheimer’s and Parkinson’s, enabling the study of how these conditions progress in the brain. These models allow scientists to investigate underlying cellular changes and test treatments aimed at slowing the neurodegenerative process.
In immunology, murine models help in understanding how the immune system functions and responds to pathogens. Humanized mice, which are engineered to have components of a human immune system, have been instrumental in developing vaccines and therapies for infectious diseases. They allow for the study of human-specific infections in a controlled setting.
Metabolic diseases such as diabetes and obesity are also widely studied using murine models. By manipulating diet or genetics, scientists can create mice that develop these conditions, providing insight into the interplay of genes, diet, and lifestyle. These models are then used to test new therapeutic strategies, from medications to dietary interventions.
Creation and Development of Models
The creation of murine models has evolved from selective breeding to sophisticated genetic engineering. The oldest method is selective breeding, where animals with traits of interest are bred together over many generations to produce a strain that consistently exhibits that characteristic. This approach has been used for over a century to develop many standard inbred strains.
The advent of genetic engineering changed the landscape. Early techniques involved the random insertion of foreign DNA into a mouse zygote, which was an inefficient process. A more precise method was later developed using embryonic stem cells, where a specific gene could be targeted and modified before the cells were injected into an embryo.
More recently, gene-editing technologies like CRISPR-Cas9 have made the process faster and more accurate. Described as “molecular scissors,” CRISPR allows scientists to make precise alterations to an organism’s DNA. This technology involves injecting the CRISPR components directly into a mouse zygote, which is then implanted into a surrogate mother. This method has made creating genetically engineered mice much more accessible.
Ethical Oversight and Regulations
The use of animals in research is governed by strict ethical guidelines to ensure they are treated humanely. In the United States, every research institution using animals must have an Institutional Animal Care and Use Committee (IACUC). This committee is composed of scientists, veterinarians, and public members not affiliated with the institution. The IACUC reviews and approves all research protocols involving animals, ensuring the studies are necessary and that animal welfare is a priority.
A guiding framework for the ethical use of animals is the principle of the “Three R’s.” The first R, Replacement, calls for using non-animal methods like computer modeling or cell cultures whenever possible. The second R, Reduction, focuses on using the minimum number of animals necessary to obtain valid results.
The third R is Refinement. This principle involves modifying procedures and housing to minimize potential pain or distress for the animals. This includes providing appropriate housing and food as well as using anesthetics for potentially painful procedures. Adherence to these principles is a requirement for conducting animal research and reflects a commitment to balancing scientific discovery with compassionate care.