Model Systems Core
Impact of Model Systems on IDD Research
Animal and cellular models are revolutionizing our understanding of countless human disorders including intellectual and developmental disabilities (IDD). Such models provide fundamental insights into biological pathways and often display phenotypes that are similar to clinical indicators of the human disease or provide key insights into pathogenic mechanisms, including those that converge across disparate causal influences on IDD. Thus, animal and cellular models provide critical opportunities to identify novel targets for intervention and therefore the development of new preventive interventions and therapies. Towards this end, the overall goal of the Model Systems Core (MSC) is to seamlessly provide expertise, resources, and assessment services to WU investigators involved in the creation and evaluation of animal and cellular models of IDD.
To do so, we draw on our institutional strengths in genetics, brain imaging, bioinformatics, developmental biology and neuroscience to provide consultation, support, and specific services to WU investigators involved in understanding and treating IDD. Through these activities the MSC will inform clinical approaches to higher-impact intervention in IDD and provide access to models and techniques that can encourage scientists to expand their efforts along the lines of the primary research themes of the IDDRC@WUSTL.
Services of the Model Systems Core
Animal Behavior Unit
- Pre-Consultation Study Design to discuss issues such as background strain, littermate controls, gender effets, non-behavioral influences on performance, experimental design, and statistical power. Consultations will recommend certain tests for specific models and cost estimates for the work involved, as well as well as referrals to other relevant cores. Dr. Wozniak will also provide consultation to IDDRC Investigators on behavioral testing relevant to the Investigators own projects in their own lab.
- For Aims 2-3, the ABU will offer over 40 individual behavioral tests that fall within broad categories: 1) learning and memory – both spatial and non-spatial; 2) motor/sensorimotor functions; 3) alterations in emotionality/motivation; 4) social interactions and behaviors; 5) sensory behavioral functions; 6) depression-like behaviors; and ASD-like behaviors
- The Unit has developed a basic set of behavioral measures (e.g., locomotor activity, sensorimotor battery, Morris water maze, conditioned fear) for initial phenotyping studies that has become highly standardized and serves as a basis for determining whether more extensive testing is warranted.
- In addition, new behavioral tests were recently developed include long-term monitoring of seizure-related behaviors using a force-plate actometer, quantifying investigative rearing toward hanging objects as a measure of selective attention toward novel stimuli, marble burying for evaluating compulsive digging behavior, and an automated scoring method for the tail suspension test to assess depression-like behaviors.
Functional Assessments Unit
- Neuropathology: Consultation, advice, and assistance in developing animal and cellular models or troubleshooting techniques in the lab, basic histopathology approaches, for light microscopic evaluation, training in methods, design, analysis and interpretation, quantitative tissue analysis, ultrastructural analysis of pathological changes in the developing brain.
- Neurophysiology: Consultation and services for a wide range of in vivo and in vitro electrophysiology assays of rodent models of IDD, including EEG, Polysomnograms, Somatosensory evoked potentials (SSEP), Extracellular field potential recordings in vivo and in brain slices, Microelectrode array (MEA) recordings in brain slices and cultured cells, and Whole-cell patch-clamp recordings in brain slices and cultured cells.
- Animal Imaging - MRI: Consultation and services for small-animal MRI, instrumentation and data collection, research protocol development, technical assistance in carrying out experiments, resources for data analysis, support for statistical analysis, and assistance with grant applications and manuscript preparation.
- Animal Imaging - fcOIS: Consultation and services small animal fcOIS mapping, a recently validated method of imaging spontaneous brain activity using a high-performance reflectance optical imaging system (similar to the BOLD effect on MRI); including Awake fcOIS and Metabolic and Cerebral blood flow contrasts.
Joint consultation with the Human Genomic Characterization Unit of the Clinical Translation Core
Fees for Core Usage
Fees for utilization of the Model Systems Core are determined after initial consultation on the study design. IDDRC Members may be eligible for negotiated/reduced rates.