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Aug 5, 2014

Same Data, Opposite Conclusion: Mice Really Are Models of Human Inflammation

Same Data, Opposite Conclusion: Mice Really Are Models of Human Inflammation

Source: © KaYann - Fotolia.com

  • When a paper cautioned that mouse models might misrepresent the genomics of human inflammatory diseases, both scientists and the general public took notice. Mouse models, after all, are essential tools medical research. Any doubt over such models was bound to arouse controversy, not to mention anxiety.

    But now, after 18 months of handwringing, some of it on display in the New York Times and other mainstream news sources, another study has revisited the issue. This study, which appeared August 4 in the Proceedings of the National Academy of Sciences, asserts that the original study may have been faulty. The new study, in fact, concludes that mice models really are representative of human inflammatory diseases.

    The study’s authors—Keizo Takao, Ph.D., and Tsuyoshi Miyakawa, Ph.D., of the National Institute for Physiological Sciences and Fujita Health University, respectively—wrote that “gene expression patterns in mouse models closely recapitulate those in human inflammatory conditions and strongly argue for the utility of mice as animal models of human disorders.”

    These researchers reported that they reevaluated the same gene expression datasets used in the previous study by focusing on genes whose expression levels were significantly changed in both humans and mice. The previous study, by Seok et al., also appeared in the Proceedings of the National Academy of Sciences.

    “One of the authors of Seok et al. stated in an interview with the New York Times that when the article was rejected by Nature and Science, they received comments such as ‘It has to be wrong,’” said Dr. Miyakawa. “I had the same impression as the reviewers.”

    According to Drs. Takao and Miyakawa, 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. These researchers added that in the previous study, a comparison of the genomic response between humans and mice, including those genes altered in one species but not in another, obscured the correlation between homologous genes of humans and mice to nearly zero.

    In their paper (“Genomic responses in mouse models greatly mimic human inflammatory diseases”), Drs. Takao and Miyakawa insist that, contrary to the previous findings, the gene expression levels in the mouse models “showed extraordinarily significant correlations with those of the human conditions.”

    Additional details were provided by a press release issued by Fujita Health University: “In Seok et al., comparison of the gene expression patterns between human burn and mouse models of burns, trauma, sepsis, and infection revealed a Pearson’s coefficient of correlation (R) that ranged from 0.14 to 0.28, and the percentage of genes whose expression changed in the same direction was 55% to 61%, indicating no correlation at all. In the present report, based on the same datasets used in Seok et al., the R values ranged from 0.36 to 0.59, and 77% to 93% of the genes changed in the same directions between the human disease and mouse model.”

    Meta-analysis of the original datasets, noted Drs. Takao and Miyakawa, revealed that many molecular pathways are commonly dysregulated in human diseases and mouse models. “Numerous pathways, however, are not commonly affected in human diseases and mouse models,” they elaborated. “Focusing on the commonalities between human diseases and mouse models will allow us to derive useful information for studying the pathophysiology and pathogenesis of human diseases, and for developing treatments.”


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