Animal Research Models
According to the National Institute of Health, an animal model is a “non-human species used in medical research to obtain information about a disease and its prevention, diagnosis, and treatment.” There are significant anatomical and physiological similarities between humans and animals often used in animal models. Mammals are the most common choice, and allow scientists to experiment with biomedical technologies such as testing vaccines, researching the behaviour of a species of bacteria, trying out treatments for diseases, and learning autopsies. Animals can be divided into two groups from a legal, ethical perspective, where the law requests more ethical attention from the large animal group than the small animal group requires. The small animal group includes rats, mice, guinea pigs, and rabbits. The larger animal group includes dogs, goats, and primates.
This article will summarize some commonly used animals in animal modeling. For more detailed information, please refer to the book named Commonly Used Animal Models that can be found on the National Center for Biotechnology Information.
The mouse is the most commonly used animal in biomedical research. In 2011, there were around 6.9 million mice used for research in the European Union. Usually, the laboratory mouse used is a small mammal known as the regular house mouse; they became adapted into laboratory settings in the early 1900s. Within this species, many different categories have been developed with other uses. For example, the Inbred model is used in studies that require organisms with closely related genes. Below is a table with more details on mice categories:
Image is courtesy of National Center for Biotechnology Information.
There are a few reasons for why the mouse is selected so often, including:
It is small and non-aggressive in temper so it is easy to manage
It has a short reproductive cycle so it breads and makes new generations fast
Scientists know very well about its genetics and physiology
Scientists can manipulate its genes or observe spontaneous mutations in its genes, which is useful for studies in genetics
There is a wide range of ways in which mouse models can be used. Mouse models have been used by modeling a human disease to experiment with cures for those diseases. For example, the development pathway of Parkinson’s disease can be modeled with the mouse. This includes showing how the misfolded protein that causes Parkinson’s disease spreads into the brainstem and moves up into other parts of the brain, which leads to motor deficits, depression, and memory problems. Other conditions that mice have been used to model include cystic fibrosis, diabetes, Alzheimer’s Disease, heart disease, seizures, and more. Fun fact, mouse models were used when developing and testing COVID-19 vaccines, along with a few other animal models.
The Norway Rat ranks second in the most commonly used laboratory animal, behind the house mouse. Around 1.6 million rats were used for research in the European Union in 2011. Up first, the image below distinguishes between these two species.
Image is courtesy of Catherine Song via The Spruce.
Rats were used in research starting from the early 1800s, and rat breeding started in the late 1800s. To date, there are many inbred strains providing a variety in the rats used for modeling different diseases. They are favourable in research because, like the mice, they are easily manageable and reproduce quickly. Much of their biology is known, and their response to human diseases is similar to humans. They can be used for many purposes of researching a human disease like the mouse, but they have also been heavily used in discovering and testing drugs to find out if the drugs will be suitable for humans. Although, only testing a new drug on a rat or another small animal species is usually not enough. The United States requires that any new drug be tested for toxicity on both the small animal species and the large animal species before it can be approved for human use.
A famous accomplishment of rabbit models is that it was used to develop the first rabies vaccine. At the beginning of rabbit research models in the mid-1800s, the European rabbits were regularly used. There is not much of a variance in breeding for laboratory rabbits. The New Zealand White rabbit breed is the most frequently used, followed by the Californian rabbit and the Dutch-belted rabbits.
Other unique inbred strains of rabbits are explicitly bred for individual research projects. For example, Japanese researchers produced the Watanabe heritable hyperlipidemic (WHHL) strain for modeling and researching diseases related to dyslipidemia (an abnormally high or low amount of lipids in the blood, in simple terms). The WHHL rabbit has malfunctioning low-density lipoprotein (LDL) receptors due to genetic deficiencies, so it develops hypercholesterolemia and atherosclerosis, both of which are diseases related to dyslipidemia. LDL is known as the “bad cholesterol.” Without the LDL receptors to take out LDL from the blood plasma, there will be a high LDL level in the blood that leads to a buildup of cholesterol in their arteries, leading to poor blood flow.
Dutch Belted Rabbit (American Dutch Rabbit Club).
Californian Rabbit (Wikipedia).
New Zealand White Rabbit (Charles River Laboratories).
Rabbits have a large volume of blood compared to other rodents, making them suitable for immunology research that involves finding out how human bodies make antibodies and how the immune system reacts, as the immune system works in the blood. Another everyday use for rabbit models is research with human pregnancy and teratogenic drugs. Rabbits are also larger in body size, so it is easier for researchers to insert biomedical devices or perform surgical implantations.
This animal model of a blue and yellow striped fish found in tropical, slow-moving waters gained popularity in the 1970s. The advantage of zebrafish is that they reproduce very quickly by frequently spawning batches of eggs, grow fast, and have at least one “orthologous human gene.” Two species having an orthologous gene means they diverged from a common ancestor at some point in the past, so zebrafish having orthologous human genes proves that zebrafish and humans share a common ancestor.
The Zebrafish (Shutterstock).
With this, zebrafish models were commonly used in research related to developmental biology, evolution, and the origin of life. More recently, zebrafish models are being used for the research of cell biology, biochemistry, and neurological sciences. As well, zebrafish are found to have easily manipulatable genes, so they are also used in genetic studies.
Article Author: Ivy Sun
Article Editors: Victoria Huang, Stephanie Sahadeo