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

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.

[1]  Andrew D. Steele,et al.  The power of automated high-resolution behavior analysis revealed by its application to mouse models of Huntington's and prion diseases , 2007, Proceedings of the National Academy of Sciences.

[2]  J. Crabbe,et al.  Influence of task parameters on rotarod performance and sensitivity to ethanol in mice , 2003, Behavioural Brain Research.

[3]  H. Meltzer,et al.  Psychopharmacology : the third generation of progress , 1987 .

[4]  O. Feinerman,et al.  Automated long-term tracking and social behavioural phenotyping of animal colonies within a semi-natural environment , 2013, Nature Communications.

[5]  Thomas Serre,et al.  Automated home-cage behavioural phenotyping of mice. , 2010, Nature communications.

[6]  S. Irwin,et al.  Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse , 1968, Psychopharmacologia.

[7]  D. M. Feeney,et al.  Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. , 1982, Science.

[8]  Minesh Kapadia,et al.  Altered olfactory function in the MRL model of CNS lupus , 2012, Behavioural Brain Research.

[9]  R. Palmiter,et al.  Complex I deficiency due to loss of Ndufs4 in the brain results in progressive encephalopathy resembling Leigh syndrome , 2010, Proceedings of the National Academy of Sciences.

[10]  K. Dobrenis,et al.  Early deficits in motor coordination and cognitive dysfunction in a mouse model of the neurodegenerative lysosomal storage disorder, Sandhoff disease , 2008, Behavioural Brain Research.

[11]  L. de Visser,et al.  Novel approach to the behavioural characterization of inbred mice: automated home cage observations , 2006, Genes, brain, and behavior.

[12]  A. Cressant,et al.  Computerized video analysis of social interactions in mice , 2012, Nature Methods.

[13]  Kourosh Zarringhalam,et al.  An open system for automatic home-cage behavioral analysis and its application to male and female mouse models of Huntington's disease , 2012, Behavioural Brain Research.

[14]  R. Stead,et al.  A behavioral profile of autoimmune lupus-prone MRL mice , 1992, Brain, Behavior, and Immunity.

[15]  Jack W. Tsao,et al.  What's wrong with my mouse: Behavioral phenotyping of transgenic and knockout mice, J. Crawley. Wiley-Interscience, Hoboken, NJ (2007), 523 pages, $99.95 , 2008 .

[16]  J. Krystal,et al.  Psychopharmacology: The Third Generation of Progress , 1989, The Yale Journal of Biology and Medicine.

[17]  J. Crawley.  Behavioral Phenotyping of Transgenic and Knockout Mice , 1999 .

[18]  Jacqueline N. Crawley,et al.  Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains , 2007, Behavioural Brain Research.

[19]  Minesh Kapadia,et al.  Autoimmune and inflammatory mechanisms of CNS damage , 2011, Progress in Neurobiology.

[20]  Kristin Branson,et al.  JAABA: interactive machine learning for automatic annotation of animal behavior , 2013, Nature Methods.

[21]  M. Scott,et al.  Drosophila Niemann-Pick Type C-2 genes control sterol homeostasis and steroid biosynthesis: a model of human neurodegenerative disease , 2007, Development.

[22]  E. Head,et al.  Autoimmune manifestations in the 3xTg-AD model of Alzheimer's disease. , 2014, Journal of Alzheimer's disease : JAD.

[23]  J. Denburg,et al.  Spatial learning during the course of autoimmune disease in MRL mice , 1993, Behavioural Brain Research.

[24]  C. Putterman,et al.  The MRL/lpr Mouse Strain as a Model for Neuropsychiatric Systemic Lupus Erythematosus , 2011, Journal of biomedicine & biotechnology.

[25]  E. Fisher,et al.  Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment , 1997, Mammalian Genome.

[26]  G. Dawson,et al.  The mouse beam walking assay offers improved sensitivity over the mouse rotarod in determining motor coordination deficits induced by benzodiazepines , 2005, Journal of psychopharmacology.

[27]  S. Sakoda,et al.  Neuroaxonal Dystrophy Caused by Group VIA Phospholipase A2 Deficiency in Mice: A Model of Human Neurodegenerative Disease , 2008, The Journal of Neuroscience.

[28]  B. Hart,et al.  The behavior of sick animals. , 1991, The Veterinary clinics of North America. Small animal practice.

[29]  J. Denburg,et al.  Disturbed emotionality in autoimmune MRL-lpr mice , 1994, Physiology & Behavior.