Bioinformatics & Genomics Programme
Scientists from the CRG, coordinated by Roderic Guigó, are taking part in an international consortium which has found out that the mouse is a good model for certain diseases, but not others.
Over recent years, thanks to breakthroughs in biomedicine, more and more experiments require live animals. For a century already, the mouse has been the animal par excellence. It is a good vertebrate model, it has a short lifespan and can be handled easily in the laboratory. This makes it a very useful biological tool for studying human diseases, like those affecting the brain or behavioural problems, for example, as well as for testing new drugs and therapies.
Nevertheless, as Roderic Guigó, coordinator of the Bioinformatics and Genomics programme at the CRG, explains, “There is a high proportion of cases where drugs that have worked well in mice then do not function in humans”. In other words, “There are pathologies for which mice are a good model and others where they are not”. So, to what extent can we transfer the conclusions from experiments with mice to humans?
In November 2014, an international team of investigators, including a team from the CRG led by Guigó, shed light on this question in four articles published in the journal Nature.
The scientists detailed the functional regions of the mouse genome and compared them with those of humans. To do this they analysed more than 100 types of different mouse cells and tissues, including the heart, brain, blood, kidney, liver and skin. The work gave rise to a data set on the synthesis of proteins from genes and the modifications of chromatin, the way in which DNA is packed into the nucleus of the cells.
The most important finding of the comparative analysis is that there is a common “language” used by cells on a molecular level but which, at the same time, is sufficiently flexible to change its structure and adapt itself to processes and functions that differ completely between the two species. This means the mouse model is valid for diseases produced due to the malfunction of the basic cellular machinery, like cancer or cardiovascular pathologies, but this is not true for diseases with external causes that the body reacts to, i.e., infectious diseases, such as AIDS or tuberculosis.
“What intuitively seems logical is that the mouse is a good model for diseases related to genes with similar expression patterns, that is to say, that work in the same way in both humans and mice, and not if they are different”, states the coordinator of the Bioinformatics and Genomics programme at the CRG.
The work of this team of international researchers will help us understand why some drugs work differently in mice and humans, as well as enabling us to know if it would be better to use mice or different model animals to make more precise studies of human biology.
The comparison between these two genomes is part of ENCODE (the Encyclopaedia of DNA Elements), the most important international genomics research project, whose objective is to decipher the instructions encoded in the human genome and to understand how these are interpreted differently in distinct cell types. The ENCODE project, which began in 2003, is financed by the National Institutes of Health in the United States and involves some thirty centres from various different countries.
The Mouse ENCODE Consortium. “A comparative encyclopedia of DNA elements in the mouse genome”. Nature. 2014 Nov 20. 515(7527):355:64. http://dx.doi.org/10.1038/nature13992
Stergachis et al. “Conservation of trans-acting circuitry during mammalian regulatory evolution”. Nature. 2014 Nov 20. 515(7527):365-70. http://dx.doi.org/10.1038/nature13972
Cheng et al. "Principles of regulatory information conservation between mouse and human”. Nature. 2014 Nov 20. 515(7527):371-5. http://dx.doi.org/10.1038/nature13985
Pope et al. “Topologically associating domains are stable units of replication-timing regulation”. Nature. 2014 Nov 20. 515(7527):402-5. http://dx.doi.org/10.1038/nature13986