Corona Daily 414: The Model Mouse

Jackson laboratory, Maine (JAX) specializes in breeding laboratory mice. It also has facilities in China. On 3 February, Qiming Wang, a researcher in the Shanghai office emailed the American lab and described the situation in China. Every weekend he would take a bullet train to be with his family in Wuhan. Some people in his building had tasted positive. Scary time. How could JAX help?

The Jackson lab researchers discussed ways to develop new mice to understand the novel coronavirus. Someone remembered Dr Perlman’s mice. During the SARS epidemic, Stanley Perlman had genetically engineered mice. In a 2007 paper, he wrote SARS was unlikely to be the last coronavirus. His mice might be useful in future.

Since that time, Dr Perlman had cryo-preserved (stored at extremely low temperatures) vials of sperm from these mice. In February, he emptied his freezer, and sent the entire semen stock to Jackson labs. In a few weeks, with an IVF treatment for mice, hundreds of Perlman mice were born.

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For animal trials, mice are less expensive, easy to maintain, and multiply quickly. Before trying a drug or vaccine on humans, it is usually tried on mice.

Our bodies have an enzyme called ACE2. Mice don’t have this human enzyme. In 2003, SARS virus couldn’t infect them. Dr Perlman had genetically modified the mice to add the human ACE2 receptors in them. SARS ended too quickly for the Perlman mice to be used widely.

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ACE2 serves as an entry point for the novel coronavirus. With its spikes it clings to the ACE2 receptors. The 2020 Perlman mice refused to get ill with Covid-19. Scientists found out why. The human ACE-2 was added in the mice, but the mouse ACE-2 was not deducted. Also the human version of the gene was wrongly placed.

Dr Wang Youchan from Beijing succeeded in removing those shortcomings. The latest genetically modified mice have only the human ACE-2 in the exact specific location on the X chromosome. Dr Wang used a state-of-the-art gene editing technology that did not exist in the times of the Perlman mice. As far as the virus is concerned, the Dr Wang mice are almost human.

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Dr Wang’s tests show the virus attacks the mice’s lungs, tracheas (windpipes) and digestive systems. Older mice are getting more ill than younger ones. One surprising thing is that the virus is replicating in the brains of the mice. In humans, that is not detected so far, except the loss of smell in some patients. Covid-19 has not been fatal to mice, but they get sick, lose weight and develop lung damage.

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There is a huge demand for genetically modified mice. Drugs and vaccine creators order custom-made mice for diabetes, cancer, blood disorders or any other disease. China sells a pair for $17,000. Currently the market is worth $ 1.40 billion. The pups of those mice may not inherit those (artificial) traits. In other words, they may be born natural, with no human genes.

In the last three months, many universities, and research labs had to euthanize (in simple language, kill) their colonies of lab mice, because nobody could look after them. But sperm vials of the important or rare mice are usually cryo-preserved.

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Not all rodents are a menace. Lab mice sacrifice their health or life so that the human race can save itself.

Ravi