Choosing an Animal Model

As it is not always ethical to test drug treatments on humans or practical to observe patients with diseases, we've made do with the next best thing: animal models. Animal models actually date all the way back to the 2nd century, where Galen, a Greek physician and philosopher, studied apes and pigs. However, errors in his models were not noticed for a long time because he was accepted as an authority, and the church did not allow research on human cadavers. Galen incorrectly assumed that observations or data gathered from these animal models could directly translate to humans. It wasn't until the 16th century that these mistakes were corrected. By the mid 1860s, scientists like Claude Bernard, Louis Pasteur, and Robert Koch began to establish some guidelines for animal models. Pasteur and Koch, in particular, developed the germ theory of disease for studying infectious models.
While we've certainly come a long way with animal models, you still might have some basic questions about them. This is by no means the comprehensive set of rules for the model you should choose. We're covering some of the basics that are further elaborated on in The Sourcebook of Models for Biomedical Research.
I'm just starting out. How do I know what model to choose?
For disease models, you'll likely be choosing from these types:
  • Induced/Experimental: normal animals are treated surgically, genetically, or chemically to induce disease e.g., dextran sodium sulfate induced colitis.
  • Spontaneous: The animals develop the disease due to naturally occuring genetic susceptibility. Non-obese diabetic (NOD) mice are prone to developing Type 1 Diabetes and other autoimmune diseases.
  • Transgenic: DNA is inserted or deleted from the animal genome. For example, genetic mutations can be introduced to the amyloid precursor protein in mice, leading to Alzheimer’s disease pathogenesis.
  • Negative: these animals are resistant to certain stimuli or diseases. For example, rabbits won't develop gonococcal infections that typically infect other animal species.
  • Orphan: these diseases exist in an animal, but not yet in humans. Initially, scrapie in sheep was an example, but now it serves as an animal model for human encephalopathies caused by prions.
It's good to understand these terms, but how do you pick the right animal? After all, Bernard Rollin stated, "The most brilliant design, the most elegant procedures, the purest reagents, along with investigator talent, public money, and animal life are all wasted if the choice of animal is incorrect." When choosing a model, how appropriate is the analogue? The organ/tissue being studied should be functionally similar to the target's. Can you easily transfer information from one species to the next? Is it reproducible? Are animals even necessary or feasible? Finally, check the existing body of knowledge on that disease and its models. Part of your responsibility is to dig and find out what's known in the field and what work is currently being done.
What other animal factors I should take into consideration?
Genetic drift occurs when the frequency of an allele begins to change due to random sampling from the parents. In the example below, the red and blue marbles each represent a particular allele for a gene. You would pick a marble from the first bottle and place a copy of it in the second bottle. The chosen marble is placed back in the original container. In this manner, you may eventually get an entire bottle of blue marbles despite starting out with an even number of red and blue ones. This same situation can occur with your animals after several generations of breeding. This phenomenon can cause misleading results that could lead to false interpretations. You can learn more about genetic drift on Jackson Laboratories' Genetic Drift page.

Genetic drift could lead to confusing results that can be misinterpreted.
You should also be aware of any special biological properties unique to your animal model. For example, rats would be a poor choice for studying bile or bile ducts...since they don't possess a gall bladder. In another example, a published paper notes that injection of the anti-CD117 antibody, ACK2, induced anaphylaxis and death in NOD mice, but not in C57BL/6 mice. Once you understand your system, you should find out how easy it is to manipulate. Blood studies can be difficult with guinea pigs as their blood vessels are highly inaccessible. Certain animals, like prairie dogs and woodchucks, are vicious to handle. Larger animals will require more housing space and the rent for these critters can get expensive. Depending on the size of the animal, you may have to consider the types of equipment and devices used. You should also consider whether the lifespan, sex, amount of progeny, and susceptibility to disease will affect your model.
With these points in mind, you can begin to determine what animal model best suits you. But even if everything seems perfectly picked out, animal model results don't always translate well to human treatments. Why is that? Find out in our next blog! Do you have comments about animal models? Contact us here.
Contributed by Ken Lau, PhD.
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