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"I’ve been working with iTL over the past 5 years in the production of 3 different genetically altered mice. Not only did iTL help in the design of the mice, […]” - Raghu Mirmira, MD, PhD University of Chicago.
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?
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.
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.
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.
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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