Why humanized mice?
Charles E. Hewett, Ph.D.
If you read about biomedical breakthroughs, you are hearing more and more about “humanized” mice. But, what is a humanized mouse and why on earth would scientists want to experiment in this way?
Humanized mouse is a general term that refers to a mouse that has a few human cells, a short strand of human DNA, human tissues, a human tumor, a humanized immune system, or, parts of the human microbiome.
You can learn an awful lot about fundamental biology and/or genetics by studying the large number and great variety of strains of mice available to scientists today. But mice that are humanized can be even more powerful models of the human being and thus better for research into the problems of human development and disease.
Mice designed to compare tumor therapies
Take a so-called PDX mouse for example. This is a mouse engrafted with a human tumor, known as patient-derived xenograft (PDX) that is sometimes used as an avatar to guide customized patient care and more typically used to conduct pre-clinical trials for new cancer drugs. Scientists can take a tumor from a patient, cut it into pieces, and put these pieces into multiple mice. Sometimes these don’t “take” but often, each fragment grows and can then be divided into pieces and put into additional mice. Through this process, you can end up with dozens of mice, each with tumors nearly identical to each other and to the original human patient’s tumor. Scientists can treat different groups of PDX mice with alternative drugs, drug combinations, and drug sequences allowing them to determine which approach works best to eliminate a very specific tumor type.
This comparative work, for obvious ethical reasons, cannot be done in the patient from whom the tumor originated.
Mice to study the human immune system
Another powerful approach is to humanize the mouse’s immune system. In this instance, a mouse with little or no mouse immune system is injected with specific human stem cells typically derived either from fetal tissue or cord blood. These cells create human T cells, B cells and other immune cells in the mouse enabling scientists to explore how human immune systems attack a wide range of diseases including, for instance, polio, the Zika virus, cancer and others. These mice can also be used to test how well both chemical and biologically based pharmaceuticals can treat infectious diseases, different types of cancer, and irregularities of the immune system like diabetes and lupus.
Humanized mice to figure out the function of human genes in health and disease
A relatively new technique called CRISPR CAS/9 enables scientists to break a strand of DNA at a very precise location and either eliminate a short stretch of genetic code or add code from another organism. When the DNA in a mouse embryo is broken in this way and a human genetic sequence is inserted into its genome, scientists can determine whether a human gene or a specific genetic variation functions or impacts human health the way they think that it does. These mice can also be treated with alternative therapies to see if a disease causing genomic abnormality can be stopped or mitigated.
And finally, we’re learning more and more about the microbiota that inhabit each of us and play a key role in determining who we are and how we function. The micro flora and fauna that inhabit us help fight infection, control our weight, hold off diabetes, digest food properly and much more. Replacing the microbiome in a mouse with a carefully specified one derived from a human being can help us understand these functions and lead to the development of therapeutic approaches controlling or eliminating “bad” bugs and replacing them with “good” ones.
So, mice can be humanized in a wide variety of ways and, in so doing, scientists seek to learn more about how we as humans develop, grow, and fend off disease. Humanized mice also enable the testing of therapies to help us manage or cure diseases when our own systems fail us.
Charles E. Hewett, Ph.D., serves as executive vice president and chief operating officer of The Jackson Laboratory and is a member of the Laboratory's Board of Trustees. Hewett also served as a founding board member of the New York Genome Center.