How are humans different from mice?
Kirill Stasevich, "Science and Life"
The question in the title may seem idiotic without exaggeration: we all know what a mouse looks like and what a person looks like. But no one will deny that mice and humans have a lot in common, and if we go down the levels of organization, then there will be more and more of this in common.
There are not so many differences at the molecular level, after all, protein synthesis in all eukaryotes is performed by the same ribosomes. Therefore, when biologists investigate some very fundamental processes, they boldly use animal models - if some substance has affected the mouse ribosome, then it will also affect the human one.
But, of course, it is very important to understand where the similarities end – otherwise, developing drugs on mice, we can then be cruelly disappointed to find that they do not work on humans. For example, this happens with diabetes remedies: the substance works well on mice, but there is no effect on humans.
Researchers from Lund University (see the press release New research describes the differences between mice and humans) and King's College London write in their article in Scientific Reports (Amisten et al., A comparative analysis of human and mouse islet G-protein coupled receptor expression) that it's all about the characteristics of cells, synthesizing insulin. As you know, the level of sugar in the blood is very much dependent on the hormone insulin, which encourages tissues to absorb glucose. Insulin is produced by the so-called beta cells of the pancreas.
In order to synthesize the right amount of hormone and at the right time, beta cells use special receptors: a signal from the external environment, binding to the receptor, encourages cells to work more actively or, on the contrary, to suspend the synthesis of insulin. And when it comes to medications for diabetes, they often mean substances that would act on these receptors and thereby help keep insulin and sugar levels at normal levels.
Beta cells have quite a lot of receptors, and their set is similar in mice and humans. The problem is that mouse and human cells synthesize different receptors in different quantities. The authors compared the level of matrix RNAs corresponding to certain receptor proteins in mice and humans. (As we know, genetic information is first copied from DNA into an RNA molecule, and the RNA molecule then serves as a template for protein synthesis; by the level of one or another RNA, it is possible to determine the activity of a gene and estimate the amount of the corresponding finished protein.)
It turned out that some beta-cell receptor genes work very actively in mice, but are almost silent in humans. And diabetes medications that never reached the clinic were often developed, alas, just for such receptors – it is clear that they acted on mice, but they worked poorly in people who simply had almost nothing to work with.
At the same time, researchers have found a whole series of receptor proteins, which – judging by the activity of their genes – are in sufficient quantities in both human and mouse insulin-producing cells. Drug developers could pay attention to such receptors in the near future.
Of course, here you can ask why we need mice here at all. But the fact is that there is too little suitable human material, so there is no escape from animals here – you just need to understand exactly how they are similar to us and how they differ.
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10.07.2017