AG129 mice are a specialized laboratory mouse used in biomedical research, scientifically referred to as Ifnar1 & Ifngr1 dKO mice. This name signifies a specific genetic alteration that makes them useful for studying the immune system’s interaction with certain pathogens. Their unique biology allows for the investigation of diseases in a way not possible with standard mouse strains.
The Unique Biology of AG129 Mice
AG129 mice are distinct because they are genetically engineered to lack functioning receptors for interferons. Interferons are signaling proteins released by host cells in response to viruses. These proteins act as a first line of defense, triggering nearby cells to heighten their anti-viral capabilities and modulating the immune response.
These mice are deficient in the receptors for both Type I (IFN-α/β) and Type II (IFN-γ) interferons. The absence of these receptors means that even when the mouse’s cells produce interferon proteins during an infection, the cells cannot receive the signal. This disruption of the interferon signaling pathway is their defining characteristic.
This targeted immunodeficiency renders the mice highly susceptible to a range of viruses. Many viruses that cause little illness in standard mice can establish a robust infection in the AG129 model. This sensitivity is due to a precise inability to mount an early anti-viral response mediated by interferons, not a general immune system failure. Their adaptive immune system, which generates antibodies and T cell responses, remains functional.
AG129 Mice as Models for Human Viral Infections
The immune deficit in AG129 mice makes them useful for studying human viral infections that are difficult to replicate in other animal models. Researchers use them to investigate flaviviruses, a family that includes Dengue virus (DENV), Zika virus (ZIKV), West Nile virus, and Yellow Fever virus. The strong interferon response in standard mice often prevents severe disease from these viruses, limiting their research utility.
With Dengue virus, AG129 mice can develop symptoms that mirror severe human disease, including significant viremia (virus in the blood), vascular leakage, and low platelet counts. This allows scientists to study how the virus causes disease and to evaluate potential vaccines and antiviral drugs. The mice are susceptible to all four serotypes of Dengue, and certain strains can cause high mortality rates.
The AG129 model was also important for Zika virus research following its outbreak. Researchers found that AG129 mice were highly susceptible to ZIKV, which could spread to the brain and other organs. This provided a platform to test therapeutic candidates. A significant advantage of the model is its ability to develop disease from a wild-type virus without requiring viral adaptation.
Experimental Utility and Husbandry
AG129 mice can replicate complex aspects of human disease. For example, they have been used to show how pre-existing antibodies can enhance a subsequent Dengue infection, a phenomenon thought to contribute to severe dengue in humans. This allows for detailed investigation into the mechanisms of viral pathogenesis.
The immunocompromised state of AG129 mice necessitates specialized care. They must be maintained in strict specific-pathogen-free (SPF) environments with sterilized caging, food, water, and filtered air. This prevents opportunistic infections from microbes that could be lethal to an AG129 mouse but would not harm a normal one.
This susceptibility brings ethical considerations, as research requires careful oversight to minimize suffering. A limitation of the model is that a viral infection in an AG129 mouse is not identical to one in a human. Despite this, the insights gained from these mice are valuable for developing treatments and vaccines for challenging human diseases.