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Why Make A Humanized Mouse?

Last Updated on April 28, 2023 by ingenious

Why Make a Humanized Mouse?

Humanized Mouse Models

The mouse has been used for over 30 years as a model system for studying human disease. Recently, “humanized” mice have grown in popularity because they are formidable models of the human being and therefore extremely useful for understanding the human condition. What exactly is a humanized mouse? A humanized mouse is a mouse that carries functional human genes, cells, tissues, and/or organs. There are many ways to study human disease. So why do researchers make humanized mouse models in particular?

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The mouse as a model system in human disease research

It has been shown through decades of research that humans and mice share many common similarities in terms of anatomy, physiology and genetics. Although we do not look alike, on a genetic level mouse genes are very similar to our own, making mouse genetic research useful for studying human disease. By utilizing humanized mice, we have gained valuable insight into how human systems work which has allowed us to develop new and important therapies.

Some facts about mice that you may not know:

  • Adult mice multiply quickly. They can reproduce as often as every three weeks, and they can mate on the day they give birth – very different than humans but extremely beneficial to our understanding of human disease. Scientists are easily able to generate a lot of mice to work with.
  • The mouse is small compared to other potential animal models, which makes them more convenient to take care of for research purposes.
  • The time between a mouse being born and giving birth is short, usually about 10 weeks (compared to humans where it takes us about 10 months to deliver a baby). This means several mouse generations can be observed at once.
  • The mouse has a short lifespan of one year, which in terms of aging equals about 30 human years. This gives scientists the ability to measure the effects of human aging more easily by using mice.
  • Mice are used to study complex biological systems found in humans, such as the immune, hormonal, nervous, cardiovascular and skeletal systems. This is because like humans, mice naturally develop diseases that affect these systems too – including diseases such as cancer and diabetes. Also, mice can get infected with the same viruses as humans, such as HIV or COVID-19, and so mice can be studied to develop better human therapies for these viruses.
  • Compared to other potential animal model systems, it is relatively easy to manipulate the mouse genome, for example, adding or removing a gene to better understand its role in the body. This ability has provided an enormously powerful tool for modeling specific diseases when a mutated human gene can be observed in the mouse.
  • Humanized mouse models are extremely useful for studying complex diseases, such as atherosclerosis and hypertension, as many of the genes responsible for these diseases are shared between mice and humans. Research in mice provides insights into the genetic risk factors for these diseases in humans.

3 main types of humanized mice

Tumor mouse models

Immunodeficient mice (mice without a fully functioning immune system) can be used as hosts to grow both normal and diseased human tissue. Most notable, patient-derived xenograft (PDX) mouse models involve the direct transfer of human tumors into immunodeficient mice following surgical removal of the tumor/cells from the patient. The PDX mouse can be used in precision medicine, which is the customization of treatments that are tailored specifically to the patient instead of a one‐drug‐fits‐all model. For example, the PDX mouse can be used in individualized cancer therapy and drug development that specifically meets the need of the human patient to which the cancer came from rather than a more generalized approach that would be used without the aid of the PDX model.

Immune system mice

Humanized immune system mice, or models that express human versions of mouse immune genes, can be used to model the human immune system, enabling the evaluation of therapies relevant to human health in an in vivo environment. More recently, mice with humanized immune systems have been used in COVID-19 studies in order to evaluate treatments and develop vaccines during the pandemic. These models often target the ACE2 receptor, also humanized in the mouse, allowing for a more accurate human infection that scientists can study.

Gene targeted mice

Many human diseases are known to be caused in part by specific mutations in human genes. In order to better understand how mutation leads to disease, mouse models can be made in which the human mutation is inserted into the analogous mouse gene. This is achieved through a process called gene targeting, where a portion of the mouse gene is replaced with a homologous piece of DNA containing the human mutation. The subsequent mouse offspring can be utilized to study the human mutation, determine the course of disease and test potential therapies for the disease.

One example of how mouse models can be used to study human disease is in a recent publication by Ann-Louise Vikberg, et. al., from the University of Umeå, Sweden. A human mutation in the Kif23 gene is known to cause a rare form of congenital anemia and a prevalence for blood cancers. The group created a mouse model through ingenious targeting laboratory where the human mutation was inserted into the analogous mouse gene. The humanized mouse model was used to study the mutant Kif23 gene in different tissue types including bone marrow, a difficult tissue to study in humans. The ability to use the humanized mouse model as a means of studying the mutant gene in this difficult tissue type allowed the researchers to gain insights that they would not have been able to gain easily from human patients, concluding that tissue-specific expression of KIF23 variants can influence the anemia phenotype.

These reasons, and more, put humanized mouse models at the top of the list as the animal model of choice for studying human disease. Interested in using a custom mouse model in your next research project? Get a quote from ingenious today.


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