Lab rats and mice have been used for decades to make great medical advances, from HIV antiretrovirals to the flu vaccine. But there’s always been an interesting debate about which is the more useful animal model — the rat or the mouse.
With the current devastating emergence of the coronavirus pathogen, flexible research models have never been more important. Let’s take a closer look at the story behind the debate to see if 2020 will indeed be the year of the lab rat.
What does history tell us?
Rats were originally the preferred model for researchers, but then the ability to manipulate the mouse genome and embryonic stem cells was discovered, allowing easy genetic manipulation in the study of health and disease. Thus, the mouse became the preferred model in the 1980s and 1990s. Multiple mouse publications created a plethora of historical data, particularly in areas such as oncology.
However, the last decade has seen an increase in rat interest. Advances in gene-editing techniques – such as CRISPR/Cas9, TALENS, zinc-finger nucleases and the mapping of the rat genome – have been the catalyst for change. But these advances aren’t the only cause for renewed interest. Let’s look at five additional reasons:
- Rats translate better to humans
Rats are ten times bigger than a mouse, so their physiology more closely resembles that of a human. This behavioral similarity is helpful in neuroscience, particularly in work on autism. Rats are more sociable than mice, and juvenile rats play and wrestle with each other the same way kids do. Mice don’t do this. In a knockout model for autism where the gene protein neuroligin 3 is removed in rats, this play is disrupted — similarly to a human.
- Easier surgery
It’s easier to perform surgery on rats because they’re bigger than mice. Plus, you can microinject into tiny areas (such as the brain nuclei) more easily with a bigger brain. Imaging is easier as their greater size allows better resolution. You can also draw three times more blood from a rat compared to a mouse, so you can use fewer rats to get your toxicology results. Easier surgery, imaging, and blood drawing means fewer errors and saving money, time, and animals.
- Colonies can be created quickly
Knockout and knockin rat models can be created in as few as six months — that’s half the time it takes to create mouse models from traditional ES cell technology. Genomic editing tools like CRISPR/Cas9 and zinc-finger nucleases can be injected directly into fertilized embryos, eliminating the need for embryonic cells.
- Allows for more efficient animal studies
Efficacy testing has traditionally been done in mice, followed by a switch back to the rat with its historical safety data. With the advent of genetically-modified rat models, safety and efficacy testing can be done in the same rat model, even the same background strain. This avoids the mouse altogether and reduces the number of animals needed. This supports the principles of the ‘3Rs’ in animal testing, and still offers enough data to answer the research question.
- Easier handling
Rats get less stressed than mice, so they’re easier to handle. More docile than mice, they’re less likely to bite. Rats can even be trained to keep still for certain procedures and don’t need sedation like mice, which saves time and cost.
So, why use mice?
People were not led to choose mice over rats in the past purely because of the ability to manipulate the genome. Continue reading to learn about other factors that come into play when selecting a research model.
- Perception that rats are more expensive
If a research department has a history of mouse usage with mouse infrastructure in place, then changing over to rats can be expensive.
- Drug administration costs
It’s a little more expensive to perform a study in a rat, depending on drug quantities. This can be unattractive to researchers if a drug is expensive to make. However, if you get higher quality data from a rat study, then it may be considered a risk worth taking. It’s only likely to be an issue in specialized, expensive research testing.
- Mice and mice data are easily available
In general, mice are more readily available. The mouse is still the preferred species in areas such as oncology due to the sheer volume of historical data to build further research upon. While the rat model was initially the most popular model, the last 30 years have seen the mouse model rise to dominance, with a great deal more data generated from mice than from rats.
- Natural conservatism
There has always been a strong precedent in industry to use what is known.
So, what will the future hold? Now that gene-editing technology is available for both mice and rats, researchers have more choice than ever. It’s entirely possible that 2020 will prove to be the year of the lab rat.
If you have any questions on your upcoming selection of rat strains, please speak to an expert.