The results of studies on mice can not always be transferred to humans
A man instead of a laboratory mouse
Nadezhda Markina, <url>Scientists have questioned the fact that the results of studies on mice can always be transferred to humans.
The reason for the doubt is that the work of genes in mice and humans is regulated differently.
Almost all discoveries in biomedicine for the benefit of people are made on mice. On mice, scientists simulate various human diseases, test new drugs. This is the simplest and most accessible model of all laboratory animals – it is simply impossible to conduct mass experiments on the same monkeys in order to obtain statistically significant data. But the results of recent studies, published in several articles in the journal Nature, cast doubt on the fact that everything obtained on mice can be transferred to humans.
The International Consortium of Researchers (Mouse ENCODE Consortium) presented data on the ENCODE project (Encyclopedia of DNA Elements), that is, an encyclopedia of DNA elements for mice. This project describes the regulators and switches of the genes in the mouse genome. Interestingly, scientists figured out the human genome at this level earlier – the results of the ENCODE project for humans were published in 2012.
Genome sequencing is not its decoding, but only reading the sequence of letters-nucleotides (A, T, G, C) in the DNA chain. The result of sequencing is a "tracing paper", a drawing of a device that does not have instructions attached to it, so it is unclear how it works.
Creating such an instruction or "user manual" is a much more difficult task. And that's what the ENCODE project is trying to solve for both humans and mice.
According to the set of genes, humans and mice are almost the same. At the same time, the difference is obvious: the fact that we are not like mice, we should be grateful to the regulatory elements of the genome, which determine which genes, at what time and how they work. "Newspaper.Ru" has already written about another project, Fantom (Functional ANnoTation Of Mammals), in which Russian scientists from the Institute of General Genetics of the Russian Academy of Sciences are also taking part. The task of the project at its fifth stage (Fantom 5) was a comparative analysis of the work of genes in various tissues of the human body.
To some extent, ENCODE and Fantom projects solve the same tasks, but if Fantom moved from mouse to person, then ENCODE moved from person to mouse. The ENCODE project, what's for humans, what's for mice, is coordinated by the National Human Genome Research Institute in the USA.
Mice are not our closest relatives, we share about half of our DNA with them – for comparison, our DNA matches 96% with chimpanzees. Although if we take only the coding part of the genome, which carries information about proteins, the similarity of humans and mice reaches 70% in it.
But this coding part is only 1.5% of the entire DNA. And the rest of the DNA, which was previously considered "junk", is exactly what a consortium of scientists is looking for gold in this garbage – regulators of the work of genes.
Initially, scientists assumed that regulators, as well as coding genes, should be conservative to a certain extent. It turned out that this was not the case. The main conclusion that can be drawn from the articles presented in the latest Nature is that many mouse genes are regulated in a completely different way than human genes.
"For a long time we believed that all the research done on mice could be transferred to humans," says Bing Ren, professor at the Ludwig Institute for Cancer Research at the University of California, San Diego. – But this message is not always true. We found quite a few genes that are regulated differently in humans and mice. These genes are grouped into certain clusters, so, for example, a cluster of immune system genes belongs to them."
Using the same set of methods as in the human project, the researchers analyzed the work of genes in 124 different types of mouse cells in the brain, heart, blood, kidney, liver and skin. To their surprise, it turned out that in a large number of cases, regulators of gene activity in the same human and mouse tissues work differently.
According to the regulation of genes, different mouse tissues are more similar to each other than the same mouse and human tissues. For example, in mouse brain cells, the work of genes is more similar to the work of genes of mouse intestinal cells than to the work of genes of human brain cells. The regulation of mouse and human genes may differ in details, for example, the same regulator – the transcription factor may be located in different places of the genome in humans and mice.
"The useful result of the work is that now we know exactly where and how much a person differs from a mouse, so we can take these differences into account. For some diseases, we will have to create new models on other animals, but for others, mice are quite suitable," Bing Ren summed up.
The Mouse ENCODE consortium includes employees of more than 30 scientific organizations. The teams that published the articles in Nature, in addition to the aforementioned Bing Ren, are led by John Stamatoyannopolos, a professor at the University of Washington in Seattle, Michael Snyder, a professor at Stanford University, and David Gilbert, a professor at the University of Florida. They also published the results of the ENCODE for human project in leading scientific journals two years ago. Now, in addition to Nature, several articles with the results of the ENCODE for mouse project have been published in the journals PNAS and Science.
Portal "Eternal youth" http://vechnayamolodost.ru20.11.2014