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March 31, 2020

Is this lab animal the key to finding a coronavirus treatment?

Daily Briefing

    Researchers say there's no perfect lab testing animal for the new coronavirus, but this genetically engineered strain of mice might be the best fit for finding a cure, James Gorman reports for the New York Times.

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    Researchers look to mice

    According to Gorman, researchers have multiple criteria for what makes an animal useful in testing potential therapies and vaccines, and mice get high marks when it comes to the new coronavirus, SARS-CoV-2.

    But why mice?

    First, the animals that researchers study have to be susceptible to the infection in question—and not every animal is susceptible to the new coronavirus.

    In addition, the animals not only have to be susceptible to the infection, but they also have to get sick when they're exposed to the infection so scientists can determine if the treatment is stopping the symptoms, according to Gorman.  

    According to Stanley Perlman, a microbiologist at the University of Iowa, a lot of animals "don't care at all that they're infected."

    Gorman reports that the animal used to test COVID-19 treatments would also have to get sick in a way similar to humans.

    Why this genetically engineered mouse might be especially useful

    The hACE2 mouse, which Perlman engineered in 2003, appears to fit the bill.

    The hACE2 mouse is susceptible to the SARS virus and can get infected with SARS-CoV-2, too. This is because hACE2 mice have a human receptor on their cells called the ACE2 receptor.

    However, while the hACE2 mice can get sick with SARS, in the past when they've been exposed to SARS, they also "developed a brain disease" and other symptoms, which made them more difficult to study, Perlman said.

    But early research suggests the "brain disease" may not be an issue for mice with COVID-19. A study from China found that the hACE2 mice can get infected with the new coronavirus, and there was no mention of any brain disease symptoms.

    Now, researchers around the world are aiming to use the hACE2 mice in some of the first experiments for COVID-19.

    "There's a huge demand," for the mice, said Cat Lutz, director of the Jackson Laboratory, which breeds laboratory animals, "not only in the United States, but globally."

    First, researchers are going to breed the mice using frozen sperm and embryos that were put on ice after the SARS outbreak. Lutz, who is responsible for breeding thousands of mice strains, including hACE2, said she plans to have the hACE2 mice ready for distribution by May.

    But Lutz said researchers will also be looking into other ways to make mice susceptible to the new virus. "There's never only one mouse model that we use," for each disease, Lutz said. "And I think the same is going to be true in this circumstance as well."

    After mice, researchers will turn to these animals

    After testing is performed in the hACE2 mice, researchers will likely begin testing on other animals, possibly including hamsters, ferrets, and especially monkeys, who are the most likely to replicate how the disease transgresses in humans, Gorman reports.  

    Dave O'Connor, a pathologist at the University of Wisconsin-Madison, is currently assessing the suitability of studying COVID-19 in monkeys. O'Connor said a group of Chinese researchers have already started assessing rhesus macaques, and that the rest of the world would soon follow suit.

    But O'Connor noted these experiments are for determining which animal is best for testing a cure, not finding the cure itself. "We are potentially going to be dealing with this for a really long time and need to come to better terms with that," he said (Gorman, New York Times, 3/14).

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