Building a colony of hACE2 mice for COVID-19 research
JAX has created a new colony of specialized hACE2 mice to support global research on COVID-19. hACE2 mice are available for order, and JAX will begin shipping in June 2020.
As labs worldwide halt research, a Jackson Laboratory team is reaching out to help.
Rob Taft’s job is saving lab mouse strains. As senior services program manager at The Jackson Laboratory (JAX), Taft ensures that valuable strains of laboratory mice are conserved as cryopreserved (frozen) embryos and sperm, to enable scientific continuity and that years – sometimes decades – of valuable research won’t be lost. His team’s work enables JAX to maintain a collection of more than 11,500 strains to help researchers find the right mouse model for their research.
The COVID-19 pandemic has made rescuing mice and mouse strains an emergency mission. “The current situation is impacting research across the country and around the world as we all implement measures to slow COVID-19,” Taft says. “The adoption of physical distancing and shelter-in-place orders means that many research activities are having to be suspended.”
Organizations using animals are required to have disaster plans to ensure the humane treatment of animals and continuity of research, he notes. “However, the current situation is creating concern that novel mouse strains that may hold the key to new treatments for disease could be lost to science.”
JAX has mounted mouse rescue efforts in the past, such as in Houston in 2001 following flooding caused by Tropical Storm Allison, and in the New York City area in the wake of Hurricane Sandy in 2012, but never before on this nationwide and even international scale.
“As we saw how the situation was evolving, we formed a team to focus on this and began developing plans to help the scientific community protect strains critical to research,” Taft says. Recognizing that researchers in cities around the country need to quickly cryopreserve their strains, the team decided to send trucks to pick up the mice and bring them back to JAX to have their sperm or embryos frozen. Trucks are now on their way to cities on the East Coast; additional pickups are planned for the West Coast and other areas hit hard by the pandemic.
“After hearing from the research community that some organizations were stopping all nonessential work in places like New York City and Boston, we proactively scheduled trucks to be in those areas ahead of the deadlines to pick up mouse strains and bring them back to JAX for cryopreservation,” Taft says. “We’re also making changes to accommodate a much higher-than-normal pace of receiving animals and cryopreserving strains so that we can accommodate as many requests as possible.”
Michelle Burns, a technologist in The Jackson Laboratory's cryopreservation services unit, looks over frozen genetic samples of research mouse strains in a cryopreservation tank. JAX photo by Tiffany Laufer.
JAX is also ready to rush
to labs around the world so that researchers can freeze mouse sperm quickly and send it back to Bar Harbor for safekeeping. Special, high-volume kits are available that can process up to 50 strains. JAX is keeping the cost of providing these emergency services as low as possible, in line with its nonprofit mission.
Cryopreservation enables JAX to serve as the world’s repository of genetically defined laboratory mice, a kind of seed bank for ensuring that mouse strains are available to researchers in perpetuity. Only those strains that are actually needed for research programs are maintained in live colonies, says Cat Lutz, Ph.D.The primary research goals of the Lutz lab involve developing preclinical mouse models of neurodegeneration to test therapeutics and inform clinical trials.Cat Lutz,
senior director of the JAX mouse repository and in vivo pharmacology. For all other strains, “we put them in cryopreservation, and this is very much like you would see in a human IVF clinic. Sperm and embryos are cryopreserved, and they're able to be reanimated at any time. So if a particular researcher is looking to have a mouse model for a particular disease that hasn't been utilized in a long time, we can just reanimate that strain from the freezer.”
Developed in the early 1970s, embryo cryopreservation was quickly adopted by Wesley Whitten, Larry Mobraaten and other JAX scientists to establish the first embryo cryopreservation program. The ability to cryopreserve embryos meant that hundreds of embryos could be stored in containers similar in size to a cocktail swizzle stick, with hundreds of thousands stored in a single tank maintained in liquid nitrogen at -196º Celsius. Samples of each mouse strain cryopreserved in Bar Harbor are also sent to a back-up “mirror” site, protecting strains from being lost during disasters and enabling strains not actively used to be stored until they are needed.
The cryopreservation and in vitro fertilization techniques perfected at JAX also became essential to human fertility treatments. Ironically, freezing human sperm was initially much more effective than freezing mouse sperm, which would lose almost all its viability after being thawed. In 2007 Taft and other JAX scientists figured out the exact process required. Since a single male mouse can produce millions of germ cells, sperm cryopreservation is a highly efficient way to capture and preserve the genetic profile of a mouse strain.
Taft’s message to the research community: “We’re still here, we’re still open, and we’re here to help.” For those already impacted by shelter-in-place orders, he says, “we may be able to work with your facility staff to get animals out. For those who are waiting, please be aware that the situation can change very quickly.”
And once labs are ready to reopen, Taft says, “with our special expertise, JAX will be here to help the world’s research community to rebuild their mouse colonies, and get back to their important work of finding cures and treatments to improve human health.”