The use of rodents and mice has been monumental in understanding and learning about
immunology and Human Immunology. Due to the number of mice and how quickly they can
reproduce allows for a constant supply of test subjects. Mice can be used by scientists in order to
learn further about the immune systems of not just humans but mammals in general. Mice and
Humans are incredibly similar biologically and genetically. Humans and Mice share the same
gene functions and develop in similar ways. Mice are the best models that can be used to study
human immunology.
Mice have been used and studied in laboratories for the last 100 years, more information
is known about their genetics and biology than any other animals except humans. Mice have
been used because of how similar their development to humans is and as well as how some of
their genes are expressed. Due to this extensive research, there are thousands of laboratory
mouse stains that are readily available that can be used to study different diseases and how
different diseases are processed.
The mouse Encode project is a Databank of DNA Elements whose purpose is to examine
the genetic and biochemical processes involved in the regulating of mouse and human genomes.
This database includes the genes that build proteins, non-protein coding genes, and regulatory
elements that control when genes are activated and turned off in different tissues and cells.
Through the Encode project, researchers have found that mice and humans have a general level
of gene regulation, development of organs, and heredity.1
Mice have incredibly short life spans compared to humans, domestically they only live 1
to 3 years. This is a benefit to scientists and researchers because it allows them to see how a
1 U.S. Department of Health and Human Services. (2015, December 3). Comparing the mouse
and human genomes. National Institutes of Health. https://www.nih.gov/news-events/nih-
research-matters/comparing-mouse-human-genomes
disease affects the animal throughout its life. This is incredibly useful to be able to run tests on
the animals at different stages of their life. This is seen in diseases such as Cancer, Alzheimer’s,
and other chronic diseases.
Mice and humans share effectively the same set of genes. Almost every gene found in
one species has been present in some form in the other. Roughly 4000 genes have been studied
and less than 10 of the genes are exclusive to one species. On average the protein-coding regions
of humans and mice are 85% identical. Other genes are even 99% matches and others are only a
60% match. These regions are similar in humans and mice because they are required for
function. What this shows is that when a particular DNA region is compared, the functional
regions stand out due to their incredible similarity. According to evolutionists, humans, mice,
and other mammals shared a common ancestor approximately 80 million years ago.2 This means
that all mammals are able to be compared to one another, however, the mouse is the one that is
used because it is the most well-developed experimental model. Furthermore, it is the easiest
model to manipulate because the genes can be easily found and tested. Researchers can
manipulate the gene and cause it to emulate the effect of DNA changes and alterations. This is
seen commonly when scientists are studying diseases such as Alzheimer's, cancer, heart diseases,
and many other deadly diseases.
Genetically altered mice are used in Alzheimer's research, the mice are genetically altered
with Familial Alzheimer's Disease. This causes the formation of amyloid plaques, which are the
aggregates of misfolded proteins that form in the spaces between nerve cells. Treatment is very
successful in the Mouse Model but the human model yields low to no success. While the Human
model’s results appear to be disappointing, every failed test allows for more knowledge to be
2 Why mouse matters. Genome.gov. (n.d.). https://www.genome.gov/10001345/importance-of-
mouse-genome
learned and what does and doesn't work when trying to find a cure or a treatment. In the case of
the mice with Familial Alzheimer's Disease, it was discovered that the exportation of
phosphodiesterase 4D5 (PDE4D5) to the G-protein receptor kinase is required for the neuron to
be activated correctly. The lack of phosphorylation did reveal that the neuron could not follow
the normal signaling pathway. This is almost identical to the early stages of Alzheimer's in
humans. When the mice were given a PDE4 inhibitor, a drug that is comparable to the
exportation of PDE4D5, it resulted in the mice having a greater ability to learn and retain
memories. However, the use of PDE inhibitors in treating Alzheimer's has been varied but still
remains to be a potential treatment if explored further. A study was done with the popular PDE5
inhibitor sildenafil, known as Viagra. It originally showed a reduced risk of Alzheimer’s when
taking the drug, however, a later study showed there was no correlation between the two.3
Even though there is a large size difference between the two species, mice develop cancer
at the same rate as humans. They develop tumors in the same tissues and the tumors have the
same make-up as tumors in humans. While the cancer takes effect and spreads much quicker in
the mouse, it progresses almost identically to a human with the same kind of cancer. With mice,
the cancer can become malignant and create multiple genetic alterations within the span of 6 to
18 months, whereas in humans it can take years for a tumor to appear and become malignant.
The mutation frequency is similar between the two species, it is much easier for the cells of the
mouse to become mutated and transformed in a culture. The cause of this is believed to be that
the mouse has a weaker and less efficient DNA repair, less genetic stability, or errors in DNA
3 Howard, L. (2023, June 4). New Mouse Study reveals a key process in how the Brain Forms
Memories. news. https://health.ucdavis.edu/news/headlines/new-mouse-study-reveals-a-key-
process-in-how-the-brain-forms-memories-/2023/03#:~:text=The%20researchers%20found
%20that%2C%20as,early%20stages%20of%20Alzheimer’s%20disease.
methylation. 4
There are a large amount of differences that can not be ignored between the human and
mouse models. Mice have a significant bronchus-associated lymphoid tissue, this allows the
acquisition of “antigens from the airways and initiates local immune responses and maintains
memory cells in the lungs”. The balances of neutrophils and lymphocytes are different between
the two species. Mouse blood contains more lymphocytes, the composition of the blood is 75%-
90% lymphocytes and 10%-25% neutrophils. Human blood contains more neutrophils and its
composition is 50%-70% neutrophils and 30%-50% lymphocytes.
In regards to innate immunity, the main difference between mice and humans, the Paneth
cells located in the small intestine of mice express over 20 defensins in particular cryptidins.
Humans only express 2 defensins. Paneth cells produce antimicrobial peptides and proteins that
are important for host defense.
Adaptive immunity differs heavily between the two species. The FcR is expressed in
several different ways between the two. Mice lacking FcaRI (CD89) is an important IgA
receptor, mice however lack this and instead use other receptors such as Fcα/μR, CD71, and
polymeric IgR. Humans have two IgA receptors that are not present in mice, FcγRIIA and
FcγRIIC.
5The Mouse is the best model that can be used to study human immunology. It is the most
widely known and researched experimental model to date, it has been studied and researched for
the past hundred years. Due to the mouse and human having a common ancestor that dates back
4 Balmain, A., & Harris, C. (n.d.). Carcinogenesis in mouse and human cells: parallels and
paradoxes. https://doi.org/10.1093/carcin/21.3.371
5 Masopust, D., Sivula, C. P., & Jameson, S. C. (2017, July 15). Of mice, dirty mice, and men:
Using mice to understand human immunology. Journal of immunology (Baltimore, Md. : 1950).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512602/
roughly 80 million years ago, they have similar evolutionary functions. Almost every single gene
found in one species can be found in some form in the other species. Mice are readily available
and can rapidly procreate while having large litters in short succession. While the mouse does
have a much shorter lifespan compared to humans, this is incredibly beneficial because it allows
the researchers to test and evaluate different treatments for diseases at different stages in the
mouse's life. Mice are commonly used to study chronic diseases, such as Cancer, Alzheimer’s,
and many others. In the case of cancer, mice are the preferred model because the way they
develop cancer and the way the cancer grows is almost identical to that of a human. When
genetically modifying a mouse to have Familial Alzheimer's Disease, it was revealed to
researchers that if a PDE4D5 was removed, it mimicked the way neurons in an Alzheimer’s
patient behaved, and when given a PDE4 inhibitor, brain function and memory retention
improved. This revealed to the researchers that phosphorylation was the key to treating
Alzheimer's. There are some notable differences between the mouse and human models. These
include the differences in their design, such as mice having bronchus-associated lymphoid tissue,
and mice having a blood makeup that heavily favors lymphocytes over neutrophils. Regarding
the innate immune system, the main difference is that mice produce and express more cryptdins
than humans. Finally, Adaptive immunity differs heavily due to the species lacking IgA receptors
that the other species have. Despite the differences between the two models, the mouse model is
still the most suitable and best model to study immunology as well as human immunology.
Citations
Balmain, A., & Harris, C. (n.d.). Carcinogenesis in mouse and human cells: parallels and
paradoxes. https://doi.org/10.1093/carcin/21.3.371
Howard, L. (2023, June 4). New Mouse Study reveals a key process in how the Brain
Forms Memories. news. https://health.ucdavis.edu/news/headlines/new-mouse-study-
reveals-a-key-process-in-how-the-brain-forms-memories-/2023/03#:~:text=The
%20researchers%20found%20that%2C%20as,early%20stages%20of%20Alzheimer’s
%20disease.
Kennedy, B. (n.d.). Similarities and differences between mice and humans revealed. Penn
State University. https://www.psu.edu/news/research/story/similarities-and-differences-
between-mice-and-humans-revealed/
Masopust, D., Sivula, C. P., & Jameson, S. C. (2017, July 15). Of mice, dirty mice, and
men: Using mice to understand human immunology. Journal of immunology (Baltimore,
Md. : 1950). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512602/
Mestas, J., & Hughes, C. C. (2004). Of mice and not men: Differences between Mouse and
human immunology. The Journal of Immunology, 172(5), 2731–2738.
https://doi.org/10.4049/jimmunol.172.5.2731
U.S. Department of Health and Human Services. (2015, December 3). Comparing the
mouse and human genomes. National Institutes of Health. https://www.nih.gov/news-
events/nih-research-matters/comparing-mouse-human-genomes
Why are mice considered excellent models for humans?. The Jackson Laboratory. (n.d.).
https://www.jax.org/why-the-mouse/excellent-models#:~:text=And%20the%20mouse
%20genome%20is,any%20animal%20except%20for%20humans.
Why mouse matters. Genome.gov. (n.d.). https://www.genome.gov/10001345/importance-
of-mouse-genome
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