Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Abstract

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.

Differential Effects of Chronic Immunosuppression on Behavioral, Epigenetic and Alzheimer’s Disease-Associated Markers in 3xTg-AD Mice

“…In each block, mice were exposed to tests re ective of neurological/sensorimotor function, spontaneous locomotor activity and emotional reactivity. These tests were performed during the dark phase in the following order: basic re exes, beam walking, Rotarod, olfactory sensitivity, T-maze alternation, novel object, open eld, step-down, Morris water maze, and spontaneous activity, as described earlier in detail [52,65,95].…”

Development of the Digital Arthritis Index, a Novel Metric to Measure Disease Parameters in a Rat Model of Rheumatoid Arthritis

“…One of the largest challenges of drug discovery is the ability to rapidly identify compounds using in vivo disease models through phenotypic screens. In vivo animal models can be labor-intensive and can require post-mortem histopathology analysis, which may take several weeks to generate results ( Perrin, 2014 ; Sakic et al, 2015 ). Screens for RA drugs are similarly laborious, due to the limitations of current methods, such as the need to have the same trained technician perform all conventional measurements.…”

“…Phenotypic screening in animal models of disease plays a crucial role in understanding pathogenic mechanisms and developing novel therapeutics. However, several challenges remain with using current clinical methods to evaluate disease in these animal models, including the subjective nature of semi-quantitative, scoring-based methods ( Crabbe et al, 1999 ; Crawley, 2008 ; Mandillo et al, 2008 ; Scott et al, 2008 ; van der Staay et al, 2009 ; Zheng et al, 2013 ; Perrin, 2014 ; Sakic et al, 2015 ), time-consuming and labor-intensive longitudinal experiments, as well as the need for better functional readouts that represent all aspects of disease, thereby enabling greater translation to human diseases ( Bendele, 2001 ; Roy et al, 2007 ; Asquith et al, 2009 ; Bevaart et al, 2010 ; Misharin et al, 2012 ). Therefore, there is a need for more consistent, automated, and clinically relevant methods to generate comparable and reproducible data for assessing disease phenotypes.…”

Differential Effects of Chronic Immunosuppression on Behavioral, Epigenetic and Alzheimer’s Disease-Associated Markers in 3xtg-AD Mice 

“…In each block, mice were exposed to tests re ective of neurological/sensorimotor function, spontaneous locomotor activity and emotional reactivity. These tests were performed during the dark phase in the following order: basic re exes, beam walking, Rotarod, olfactory sensitivity, T-maze alternation, novel object, open eld, step-down, Morris water maze, and spontaneous activity, as described earlier in detail [55,69,100].…”

“…Summary of behavioral data collected. Descriptions of methodology and variables tested are described in detail in previous reports[55,69,100].…”