Looking at the Complete Picture: Tackling Broader Factors Important for Advancing the Validity of Preclinical Models in Disease

Experimental animal research can provide focused, standardized model systems, to increase our understanding of human disease etiology and potentially discover new therapeutic targets. For example, preclinical research utilizing genetically modified mouse models has steadily increased over the last few decades, with a focus on capturing endophenotypes, rather than the full spectrum of human disease characteristics. However, preclinical animal studies often not only ignore the complexity of the human disease in question, but the sensitivity of the model system utilized (e.g. laboratory mouse or rat) to environmental factors. Many studies limit their focus to only assess some behaviors, thus missing important insights on the wider cognitive and behavioral profile. There is also increasing evidence that cage systems, handling procedures, and even the sex of the researchers carrying out the experiments, can alter the observed outcomes of the animal model system chosen. Therefore highlighting greater awareness and inclusion of these factors into experimental design is important going forward.

There remains a need for greater comprehensive, in-depth testing of disease-relevant behaviors and pathologies. For example, in mouse models of neuropsychiatric and neurodegenerative disorders, there remains a limited focus with studies predominantly only assessing certain symptom domains (e.g., hyperlocomotion and sensorimotor gating in models of schizophrenia, learning and memory in models of dementia) while neglecting others that are core to these disorders (e.g., wider cognitive and social symptoms). There is also often a lack of detail on experimental test conditions such as laboratory housing specifics (e.g. cage systems or enrichment) and handling procedures and how those factors might impact experimental test outcomes. This research topic will explore these challenges, with a goal to outline the limitations of some of the currently employed behavioral testing strategies, to provide insights into how these can impact the validity of animal models for human diseases. Ultimately, the topic aims to increase awareness of the importance of deeper considerations into the sensitivity of preclinical animal model systems to environmental influences, thus improving the translational value of these models for research into human diseases, as well as their between and within laboratory reproducibility.

The scope of this Research Topic will include original research studies:
i) utilizing more comprehensive experimental test strategies to improve disease relevance of preclinical research.
ii) evaluating the impact of laboratory environment on the validity of mouse models for brain diseases.

Furthermore, submissions providing an overview of work carried out in the field to date, as well as opinion pieces on what researchers should be aware of and address in future work, to improve the translational value of animal model studies, are encouraged.