On Mar. 25, 2020, the Jackson Laboratory (JAX) announced it was working to ensure that the worldwide research community had access to a mouse model that can serve as an accurate experimental platform for COVID-19. In 2007 Stanley Perlman and Paul McCray of the University of Iowa developed the K18-hACE2 mouse, which carries the hACE2 (human angiotensin I converting enzyme 2) gene; this is the gene that encodes the receptor that the COVID-19 binds to, infecting cells and causing illness.

To generate sufficient quantities of the K18-hACE2 mice, the JAX team immediately initiated a large-scale in vitro fertilization (IVF) program. “We are extremely fortunate to have reproductive science capabilities that far extend our capacity to generate these mice by just natural mating,” Lutz explains. “Natural mating involves putting a male and a female into a cage, giving them some time to get to know each other, and producing a small litter of pups of maybe five or six animals.”

By using IVF alongside traditional breeding, JAX has generated a new colony of hACE2 mice. The colony can now be sized to meet the demands of researchers around the world. Preliminary data, from multiple independent research institutions that have recently received cohorts of hACE2 mice from JAX, indicate that the mice are not only capable of infection by SARS-CoV-2, but also lose body weight as a result of a sustained infection that is lethal in these mice. This is similar to the results from previous research seen with SARS-CoV infection. Moreover, genetically identical mice that did not receive the virus show no signs of illness.

Lutz notes that all this extraordinary effort is more expensive to conduct than traditional breeding. “But one thing that we have committed ourselves to doing is to making sure that the price of the mice is as low as it can possibly be. This is very much in line with our nonprofit mission. We do want to lend some reassurance to the users of these animals that we are providing them not only as quickly as possible, but as cost-effectively as we possibly can, so that they can maximize the use of these animals in their research.” Thanks to the cooperation of the University of Iowa, JAX is also keeping licensing costs associated with the mice to a minimum.

Besides the efforts to breed and distribute enough K18-hACE2 mice to meet demand, JAX is reviewing other mouse models for their potential to advance COVID-19 research.