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IOWA CITY - As medical researchers worldwide began to study COVID-19 to try and develop a vaccine or other therapies to blunt the deadly disease, they soon realized common lab mice weren't useful.
'Normal mice could not be infected with the virus,” said Dr. Stanley Perlman, a University of Iowa professor of pediatrics, microbiology and immunology as well as the Mark Stinsky Chair in Virology.
Perlman and Dr. Paul McCray, also a UI professor of pediatrics, microbiology and immunology, realized they had something in their labs that might help: Decade-old frozen mouse sperm.
The researchers, along with Jincun Zhao, now at Medical University in Guangzhou, China, in 2005 developed a transgenic mouse that could be infected with SARS-CoV, a viral respiratory illness that spread to more than 8,000 people worldwide in 2003.
By the time the UI came up with the mice, the epidemic was over, Perlman said. They kept the mice around for a few years, but then decided it was easier just to preserve the sperm.
'When SARS-CoV-2 hit the population, we didn't have live mice,” Perlman said, referring to the new coronavirus that has infected more than 9 million people worldwide and killed more than 490,000 since last year. 'We had to rederive the mice, then we could study them.”
The UI has made information about how they developed the transgenic mice available for free to any other researchers who want it.
The way they did it was using an adenovirus gene therapy vector that is inhaled by the mice to deliver the human ACE2 protein into mouse airway cells. Once the airway cells have the protein, the mice become able to be infected with SARS-CoV-2 and can develop COVID-19-like lung symptoms.
Although the disease is not fatal in the mice, they do get sick, losing weight and developing lung damage.
But research on mice may be critical to ending the pandemic.
'What it allows you to do is test vaccines, test anti-viral therapies, learn how the virus is causing the disease - things you do not want to learn for the first time on people,” Perlman said.
The researchers, reporting in the journal Cell, showed these transgenic mice could be used to evaluate a vaccine and several potential COVID-19 therapies, including a preventive strategy known as poly I: C, which boosts the natural immune response, convalescent plasma from recovered COVID-19 patients, and the anti-viral drug Remdesivir.
Therapies tested on the mice so far have prevented weight loss, reduced lung disease and increased the speed of virus clearance in the mice, the UI reported.
The Iowa mouse model isn't the only one available for coronavirus research, Perlman said.
'It turns out, because COVID-19 is so important, lots of people are developing mouse models. There are several others that are similar or in some ways better or worse,” he said. But the Iowa model 'is widely used and a lot of people are interested in using it.”
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