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SP0136 Genomic Responses in Mouse Models Poorly Mimic Human Inflammatory Diseases
  1. R.G. Tompkins
  1. Surgery, Mass General Hospital/Harvard Medical School, Boston, United States

Abstract

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Our results demonstrate a lack of correlation between human inflammatory diseases and the mouse models used ultimately to create drugs to treat these diseases. Although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). Our article provides data for what most investigators already know from their experiences – current mouse models poorly reflect human inflammatory diseases. We do not damn all mouse models. Rather, we propose that the scientific community raise the bar to require model systems to more accurately reproduce the molecular features of human inflammatory disease. In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.1698

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