Mice Models

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In almost every psychology class I have had this year, my professor has provided an a mouse experiment to promote every point she made*. When I think of a laboratory, I think of fluorescent lights illuminating blue, gloved hands on a white mouse with red eyes. Lab mice are so bound up with our idea of research that  we often forget that not everything we learn from mice can be applied to humans. So how similar are our species?

Pretty similar, it turns out. Both the mouse and human genome have been mapped. There is only about an 11% difference between human and mice genes.

Despite our genomes, however, mice and humans have significant differences. The two species diverged about 90 million years ago. Because they are so small, mice evolved in a completely different world than we did. They face many challenges that we don’t, such as how to keep from getting sick when their noses are only raised an inch off the ground. Mice have a different diet than humans, which means that they have a different digestive system to break down their food.

There have been many assumptions about what is true in humans since it has been proven in mice. This is a dangerous train of thought, especially in the world of pre-clinical trials. Scientists and companies could lose money if they do not consider the differences between mice and humans. You could be led to believe science that isn’t true.

The immune system of the mouse and the human are actually quite similar. One difference is that mice have bronchus-associated lymphoid tissue. Bronchus-associated lymphoid tissue, or BALT, is a mucous membrane that recognizes germs that float down the airway and warns the immune system. Another key part of the immune system is the white blood cells. There is a different ratio of white blood cell types, specifically neutrophils and lymphocytes. Neutrophils are the white blood cell heroes of your imagination. They fight germs by swallowing them whole.

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I wish I could fight my problems by eating them, and I wish they tasted like the cinnamon sugar bagels with almond honey schmear I ate this afternoon. Lymphocytes make substances that either recognize the germ or or kill it on impact like a tracker missile. Mice have many more lymphocytes than neutrophils, but in humans they’re more equal. Both mice and humans sometimes get in more difficult situations than white blood cells can address. Mice do not always respond to acute inflammatory stress, like burns or sepsis, in the same way that humans do. Drugs that suppress sepsis in mice could actually increase the disease in humans. However, this is highly variable based on the strain of mouse, and more research is being done to find a more accurate model for inflammation in humans.

Rodents and humans have two main differences in their digestive systems. Mice usually don’t eat many fatty foods, so they don’t need a gall bladder. The gall bladder is used to store bile, which breaks up fat.

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Mice have a large intestine three times as big as their stomach with special bacteria to help break up the seeds and grains they eat. Some of my favorite new research that’s coming out is about how the bacteria that lives in the gut could influence the brain. John Cryan, a neuroscientist at University College Cork, studies the effects that different benign bacteria have on the behavior of mice. This is fascinating research, but it will be difficult to make assumptions about how the bacteria affects human behavior since rodents and humans have such different gardens of bacteria that live in our intestines.

Now for my favorite subject, the brain. About 40% of neuroscience research is done on mice, so the differences between our brains and mice brains is of monumental importance. Mice have teeny tiny brains, weighing just 0.02 ounces, whereas human brains weigh 3 pounds. Mice have a tiny intelligence to match their tiny brains. Most human brain cells resemble mice brain cells, but are larger and more sophisticated. For example, human astrocytes (a form of glial cell) are 2.6 times larger and stretch 10 times as far as mice astrocytes. There are small differences in the way the mouse and human brain is structured. Humans rely more on their visual system, while rodents tend to lean on their sense of smell. This means that humans have a larger optic cortex and mice have a larger olfactory cortex.

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Beyond that, the mouse brain is disarmingly similar to the human brain. There are differences in the permeability of the blood-brain barrier, which protects the brain from toxins coming in through the blood stream. The blood-brain barrier is the reason your brain isn’t affected when you get food poisoning, but it also makes it more difficult to create drugs that affect the brain. Some substances enter human brains more easily than mouse brains, and vice versa, which is important for scientists to keep in mind in pre-clinical trials.

This is a brief overview of the differences between mice and humans, but it is enough for me to be wary of applying mice models to human subjects. Member of the Kavli Foundation for advancing basic science for humanity, Nenad Sestan, M.D., Ph.D., explains: “There is no valid animal model that can entirely replicate some human psychiatric conditions. That is why it is so important to study what is different about human development and function.” Mice make excellent testing subjects because they are similar to humans in a lot of ways, but the slight differences can hugely affect relevant research.

*In this post, I grouped mice and rats together.

 

If You Want to Read More:

Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. 2011. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci 108: 16050–16055.

Church, D., Goodstadt, L., Hillier, L., Zody, M., Goldstein, S., She, X., Bult, C., & Agarwala, R. (2009). Lineage-specific biology revealed by a finished genome assembly of the mouse. PLOS Biology, 7(5), doi: DOI: 10.1371/journal.pbio.1000112

J. Seok et al., “Genomic responses in mouse models poorly mimic human inflammatory diseases,” Proceedings of the National Academy of Sciences, doi/10.1073/pnas.1222878110, 2013.

Kararli, T. (1995). Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharmeceutics & Drug Disposition, 16(5), doi: 351-80

Koch, C., & Reid, R. C. (2012). Table 1: Man versus mouse 
comparing the human and mouse brain reveals why mapping the mouse brain is easier. Nature, 483, 397-398. doi: 10.1038/483397a

Mestas, J., & Hughes, C. (2004). Of mice and not men: Differences between mouse and human immunology. The Journal of Immunology, 172(5), 2731-2738.

Miguel. “Difference Between a Human Digestive System and a Rat Digestive System.” DifferenceBetween.net. June 10, 2010 < http://www.differencebetween.net/science/difference-between-a-human-digestive-system-and-a-rat-digestive-system/ >.

Nancy Ann Oberheim, Takahiro Takano, Xiaoning Han, Wei He, Jane H. C. Lin, Fushun Wang, Qiwu Xu, Jeffrey D. Wyatt, Webster Pilcher, Jeffrey G. Ojemann, Bruce R. Ransom, Steven A. Goldman, and Maiken Nedergaard. Uniquely Hominid Features of Adult Human Astrocytes. Journal of Neuroscience, 2009; 29 (10): 3276 DOI: 10.1523/JNEUROSCI.4707-08.2009

Syvänen, S., Lindhe, L., Palner, M., Kornum, B., Obaidur, R., Långström, B., Knudsen, G., & Hammarlund-Udenaes, T. (1995). Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharmeceutics & Drug Disposition, 16(5), doi: 351-80

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