Infectious Disease Research
Mutant mouse strains enable scientists to study pathogens as they interact with the human immune system.
Mice with blood circulating inside them that carries functioning human genes or whose livers metabolize drugs in the same way as the human liver—these kinds of “humanized” mice are highly useful models for studying the molecular pathways of disease-causing viruses. Nicknamed “hu-mice,” these laboratory animals carry anatomically and physiologically relevant miniatures of the human immune system. This enables researchers to study the interaction of viruses with human cells and tissues in living organisms. Another advantage to hu-mice is that they are inexpensive compared to other laboratory animals used to study human disease, such as nonhuman primates, and they are easily managed.
A consortium of four Mutant Mouse Resource and Research Centers (MMRRCs) funded by ORIP collectively offer more than 10,000 mutant strains. Specimens can be provided either as actively breeding mouse colonies, frozen embryos or germplasm, and/or embryonic stem cell clones. The consortium also includes a clearinghouse—the Informatics, Coordination and Service Center—that assists researchers in identifying and ordering the particular type of mice that best suits their research purposes.
“When used as hosts for human-specific infections, humanized mice are a valuable tool in obtaining proof for both concepts and solutions in human disease prevention and treatment,” asserts Larisa Poluektova, M.D., Ph.D., who with Santhi Gorantla, Ph.D., is co-director for the Translational Mouse Model Core Facility (TMMCF) at the University of Nebraska Medical Center. Researchers at TMMCF work collaboratively on projects with NIH-funded academic institutions and investigators by making available large numbers of genetically identical hu-mice so that studies can be reproduced and compared.
Dr. Poluektova’s work with hu-mice began in 2008, creating mouse strains suitable for studying neurocognitive diseases caused by HIV. Her current work supports the development of long-acting antiretroviral drugs that can eradicate HIV from all cells and tissues. “But the study of HIV is not the primary focus at our facility,” she says. “Our interest is to continue to improve and strengthen our existing humanized mice, to be used for multiple possible applications in research studies.” She notes that hu-mice have been used to study not only HIV but a variety of other pathogens in their interactions with the human immune system, including the viruses that cause hepatitis, dengue fever, herpes, Ebola infection, and Zika infection.
Related reading:
Gorantla, S., Poluektova, L., and Gendelman, H. E. (2012). Rodent models for HIV-associated neurocognitive disorders. Trends in Neurosciences 35(3), 197–208.
Akkina, R. (2013). New generation humanized mice for virus research: Comparative aspects and future prospects, Virology (435), 14-28.