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Why mouse

Mice and rats are poorly susceptible to infection with the novel coronavirus. Theoretically, you can give them so much viral load that they have symptoms, but it will absolutely not reflect how sick people: most likely, they’ll just begin to lose weight, nothing more. This problem was faced back in 2003 when I was the first outbreak of SARS. Then also created genetically modified mice that were susceptible to this virus.

Laboratory animals, which could be used as comprehensive models for the study of coronavirus infection, virtually no. The coronavirus SARS-CoV-2 can infected ferrets, monkeys, there is evidence that hamsters are infected and able to infect each other.

But to complete the work to develop tools from COVID-19, it is necessary to observe two conditions.

  1. On the model organism should play a “human” disease — all of its pathogenesis, which is peculiar to man.

  2. To obtain statistically significant results on the safety and effectiveness of drugs or vaccines to detect even very rare side effects, need thousands, and even tens of thousands of experimental animals.

In the case of SARS-CoV-2 both of these conditions have not been met for any model organism.

Those same ferrets no ordinary human respiratory symptomatology, they are not coughing. They have implemented the gastrointestinal phenotype of the disease. And people have intestinal symptoms are not the most frequent and not the most important. Hence testing human medications for ferrets will not be quite significant.

The pathogenesis of the disease in monkeys is more similar to human, but this raises the second problem. It is very important that animal experiments were a reliable to see real deaths, real chance of side effects.

Imagine that vaccines are the probability of a serious adverse effect one in 10 thousand. You conducted an experiment on a thousand animals, a thousand people, and did not see this effect.

And then the vaccine will receive 100 thousand people – and that’s a potential ten deaths. But if we are talking about millions of people? The only reliable tool, there may be mass testing on laboratory animals.

The experiment even on a thousand monkeys impossible to imagine. Now, for example, “Vector” bought 20 monkeys, and more in then nurseries of monkeys there. Even on a thousand ferrets the study is unrealistic because it is very aggressive animals that are difficult to contain. But a thousand mice can be put into a room 20 square meters.

The difficulties of transgenesis

The “old” SARS-CoV to penetrate the cell uses the ACE2 receptor on the surface epithelium of the upper respiratory tract and lungs. In 2005-2007 year, there were created several model mice, which, unfortunately, was unsuccessful. In all cases, scientists have tried through transgenesis to Express the human ACE2 in mice, but under different regulatory elements, which would make the receptor be synthesized in larger or smaller amounts. About tissue-specific expression of ACE2 — that is, that one only came, in fact, in his lungs, the researchers thought. Therefore, the receptor was expressed and where, in theory, should not, for example, in the brain.

Due to the fact that the genetic cassette with ACE2 embedded accidentally, these mice after infection was sick in very different ways. Depending on the number ustroivshis copies of the gene or not they showed any symptoms, or Vice versa, in the throes of dying on the second or third day after infection in the first place, from brain damage.

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