Same Data, Different Conclusion

A statistical re-analysis has led scientists to conclude that mice are a suitable model organism for studying human inflammatory conditions afterall.

AsianScientist (Aug. 15, 2014) – Are mice really such a terrible model of human disease? Last year, a study published in the Proceedings of the National Academy of Science (PNAS) reported that mouse models poorly mimic human inflammatory diseases. However, a recent analysis of the same data—also published in PNAS—has reached different conclusions.

Researchers have long relied on mouse studies to understand biological phenomena. Much cheaper than conducting human studies and more flexible due to the availability of genetic tools, mouse studies are often used to test scientific ideas.

However, concern has been growing over the applicability of mouse studies to humans. In 2013, a study by led Seok Junhee from Stanford University showed that the genes involved in trauma, burns and sepsis were different in humans and mice. This finding reignited the debate in the scientific community on whether mouse models are appropriate for the study of human diseases, and also caught the attention of the media which gave the issue substantial coverage.

Unconvinced, professor Tsuyoshi Miyakawa from the Fujita Health University and associate professor Keizo Takao from the National Institute for Physiological Sciences in Japan decided to reanalyze the data. The original paper by Seok et al. compared the expression levels of genes that were altered in a particular human disease condition between humans and mice, regardless of whether the genes were changed in the mice. However, in a press release from Fujita Health University, Takao and Miyakawa said that this approach obscured the correlation between human and mouse homologous genes.

In the present report, the authors found the correlation values to be much higher, ranging from 0.36 to 0.59, with 77 percent to 93 percent of the genes changing in the same directions between the human disease and mouse model. Furthermore, the authors conducted sophisticated non-biased statistical analyses of the similarity between gene sets of humans and mice utilizing the bioinformatics tool NextBio. Non-parametric ranking analysis using NextBio demonstrated that the pattern of the gene expression changes in mouse models was highly similar to that in human burn conditions.

While acknowledging that there are numerous differences between human disease and mouse models, the authors said that their findings highlight the many commonalities and argue for the utility of mouse models in studying inflammation.

The article can be found at: Takao and Miyakawa (2014) Genomic Responses in Mouse Models Greatly Mimic Human Inflammatory Diseases.

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Copyright: Asian Scientist Magazine; Photo: Kim Carpenter/Flickr/CC.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Rebecca did her PhD at the National University of Singapore where she studied how macrophages integrate multiple signals from the toll-like receptor system. She was formerly the editor-in-chief of Asian Scientist Magazine.

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