Genomic Responses In Mouse Models Research Articles

Defining the optimal animal model for translational research using gene set enrichment analysis.

The mouse is the main model organism used to study the functions of human genes because most biological processes in the mouse are highly conserved in humans. Recent reports that compared identical transcriptomic datasets of human inflammatory diseases with datasets from mouse models using traditional gene‐to‐gene comparison techniques resulted in contradictory conclusions regarding the relevance of animal models for translational research. To reduce susceptibility to biased interpretation, all genes of interest for the biological question under investigation should be considered. Thus, standardized approaches for systematic data analysis are needed. We analyzed the same datasets using gene set enrichment analysis focusing on pathways assigned to inflammatory processes in either humans or mice. The analyses revealed a moderate overlap between all human and mouse datasets, with average positive and negative predictive values of 48 and 57% significant correlations. Subgroups of the septic mouse models (i.e., Staphylococcus aureus injection) correlated very well with most human studies. These findings support the applicability of targeted strategies to identify the optimal animal model and protocol to improve the success of translational research.

マウスはやはりヒト炎症性疾患のモデルになる―バイオインフォマティクス的手法によるマウスモデルの再評価―

マウスはやはりヒト炎症性疾患のモデルになる―バイオインフォマティクス的手法によるマウスモデルの再評価―

Genomic responses in mouse models greatly mimic human inflammatory diseases

The use of mice as animal models has long been considered essential in modern biomedical research, but the role of mouse models in research was challenged by a recent report that genomic responses in mouse models poorly mimic human inflammatory diseases. Here we 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. Contrary to the previous findings, the gene expression levels in the mouse models showed extraordinarily significant correlations with those of the human conditions (Spearman's rank correlation coefficient: 0.43-0.68; genes changed in the same direction: 77-93%; P = 6.5 × 10(-11) to 1.2 × 10(-35)). Moreover, meta-analysis of those datasets revealed a number of pathways/biogroups commonly regulated by multiple conditions in humans and mice. These findings demonstrate 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.

Modeling immunity and inflammation in stroke: differences between rodents and humans?

A recent article “Genomic responses in mouse models poorly mimic human inflammatory diseases” showed that among genes that changed significantly in humans, the murine orthologs were close to random in matching their human counterparts.1 Although this study focused on sepsis, it also raises questions about how well the rodent inflammatory response corresponds to the human inflammatory response after ischemic stroke. In this essay we argue that the peripheral inflammatory response in rodent ischemic stroke models is different than in human stroke. Given the important role of the immune system in stroke, this could be a major handicap in translating results in rodent stroke models to clinical trials in patients with stroke. Leukocyte composition in blood differs considerably in humans compared with rodents. In humans ≈50% to ≈60% of leukocytes are neutrophils and 15% to 30% are lymphocytes. In contrast, rats and mice have only 15% to 20% neutrophils and ≈60% lymphocytes. The impact of such a difference in stroke is uncertain, although certainly noteworthy. Functional differences in the immune systems of rodents and humans also exist. For example, rodents are much more resistant to infections compared with humans after surgical …

SP0136 Genomic Responses in Mouse Models Poorly Mimic Human Inflammatory Diseases

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...

Genomic responses in mouse models poorly mimic human inflammatory diseases

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. Here, we show that, 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., R(2) between 0.0 and 0.1). 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.

Of Timescales, Animal Models, and Human Disease: The 50th Anniversary of C. elegans as a Biological Model

Of Timescales, Animal Models, and Human Disease: The 50th Anniversary of C. elegans as a Biological Model