Applying the Attribute Model to Develop Behavioral Tasks that Phenocopy Human Clinical Phenotypes Using Mouse Disease Models: An Endophenotyping Approach
With the increasing sophistication of the genetic techniques used to develop mouse models of genetic disorders, it is imperative that the techniques used to elucidate the behavioral phenotypes of these models evolve just as rapidly. At present, mouse models developed to study neurodevelopmental disorders either demonstrate inconsistent phenotypes or lack behavioral phenotypes when tested using the standard battery of behavioral tasks. In this chapter, I describe a behavioral endophenotyping approach that allows researchers to explicitly model in mice the clinical phenotypes reported in human genetic disease. This approach facilitates a comprehensive approach to studying the effects of genetic mutations on behavior by individually evaluating each of the different domains/attributes of memory (e.g., time, space, sensory/perceptual, response, affect, and language), as well as social behaviors and executive function. The data obtained from this approach can be translated back to the clinical population on a per attribute basis, allowing for a dialogue between the clinic and basic science to facilitate the generation of testable hypotheses. A reciprocal interaction across levels of analysis also results in efficient development of outcome measures that can be used to evaluate the efficacy of treatment or interventional studies in the mouse model that potentially show predictive validity with later clinical trials. Examples of standardizing the behavioral phenotyping process for human disease using the NIH Toolbox, a collection of cognitive assessments, as well as a proposed murine analog of the NIH Toolbox are provided to illustrate the power of applying the attribute model to behavioral phenotyping.
KeywordsEndophenotype Attribute model NIH Toolbox Mouse model Learning and memory Task design
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