Murine “Model” Monotheism: an Iconoclast at the Altar of Mouse

Abstract

Many use mice for contemporary cardiovascular research, as we should, given the power of the genetic and other tools developed to permit rigorous mechanistic experimentation in this species. We must remain mindful, nonetheless, of the reasons why the results of mouse experiments may not extrapolate readily to human disease. Large gaps separate our mouse experiments and clinical conditions. The differences arise from the genetic homogeneity of inbred mouse strains used in experimentation, the restricted exposure of mice to many microbes and a more monotonous microbiome in mice than in free-living rodents and humans, lack of comorbidities, focus on youthful mice and exaggerated experimental conditions contrived to speed up studies, and the lack of congruence between many experimental “models” and human cardiovascular conditions. We must and should continue to mine studies on mice for the incredibly valuable mechanistic insight they provide. Yet, we as a community could consider more carefully some of the barriers to glib extrapolation of the results of experiments in mice to human disease.