Mice are of no use to research

Research team questions transferability of animal test results

02/12/2013

Studies with mice are a part of everyday medical life „They are a cornerstone of modern biomedical research, for example, to explore pathophysiological mechanisms, to evaluate new therapeutic approaches or to make pro / contra decisions with regard to new drugs“, As a team of experts around Shaw Warren of the Boston Massachusetts General Hospital currently writes in the journal "Proceedings of the National Academy of Sciences".

But how reliable are the findings from mouse experiments? The researchers asked themselves this question and formulated doubts as to whether the findings from the animal experiments could actually be applied to humans - for example, mice and humans would show completely different reactions to inflammations, the scientists say in their article. As the first research team ever, the consortium of around 20 research institutions has now compared the consequences of inflammatory processes for the genetic material of humans and mice.

Completely different reactions to inflammatory processes
Accordingly, the results from the mouse studies would rather rarely confirm in later studies with humans, which applies in particular to studies on inflammatory processes. These are involved in many diseases and injuries and change in a large part of the genome, the expression of genetic information (genotype), the so-called „gene expression“. Already in earlier studies, the scientists had found that „severe injuries would trigger a genomic storm affecting all major cellular functions and pathways“, as they write in the current article.

More than 400 people examined
For their new study, the researchers now selected 167 patients with larger wounds and 244 people with burn injuries to study the time course of altered gene activities. To do this, they repeatedly sampled white blood cells and examined them for ribonucleic acid (RNA), which is responsible for the translation of genetic information into proteins, and compared the results with the responses of three different mouse strains to similar injuries.

Finally, the investigations of the American researchers revealed something astonishing: Inflammations in humans significantly changed the expression of more than 5,500 genes. For 4900 of them, there were similar genes in mice - but their changes hardly resembled those of human genes, instead, the similarities were close to the random rate.

Strong deviations also in the reaction time
However, this is not the only finding of the scientists: For while the people were very similar regardless of the type of injury, in the rodents on the other hand, depending on the strain strong differences were observed - even with the same cause of inflammation. In addition, the researchers found large differences in the reaction time: While gene expression in the mice disappeared in most cases after a few days, this persisted in humans up to six months.

The researchers did not expect these results: "We were surprised by the weak correlation between genomic responses in mouse models and those in human injury, especially given the worldwide use of mice as models of human inflammation," said the researchers emphasize that new approaches need to be developed to improve the opportunities for human disease research.

Results so far have only been valid for inflammatory processes
In summary, Shaw Warren notes that although the findings of the study would challenge the validity of mouse models in terms of human transmissibility, it also emphasizes that the findings apply to inflammatory processes and therefore are not readily transferable to other areas of research.

For the neuroanatom Ingo Bechmann of the University of Leipzig, the result of the colleagues is also a source of great wonder: "For decades, the mouse has been the standard model of immunology that is not disturbed." As a result, the study would reveal how limited the value of experiments with mice is for different medical fields. (Sb)