Deep phenotyping of genetic mouse models of autism

  • Awarded: 2014
  • Award Type: Research
  • Award #: 313760

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental syndromes characterized by repetitive behaviors and deficits in language development and social interactions. To understand how ASDs affect behaviors in people, genetic models of ASDs in laboratory mice are needed; such models will allow researchers to test theories about how ASDs affect the brain and lead to behavioral symptoms, and will enable tests of future drugs to treat ASDs.

However, to date, good methods have not been developed to comprehensively and quantitatively characterize behaviors exhibited either by wildtype or ASD model mice. Because of this limitation, it is difficult to know whether an ASD mouse model behaves differently from wildtype mice, and if so, how different its behavior is. It is also unclear whether different ASD model mice share a common set of behavioral deficits, or whether each model has a unique pattern of behavior.

To address these issues, Sandeep Robert Datta and his colleagues at Harvard Medical School have developed two new methods for quantitating mouse behavior. First, instead of tracking mouse behavior with traditional video cameras, Datta and his team record mouse behavior with 3D cameras that capture the fine details of mouse behavior1. Second, the researchers are changing the way that the videotaped behavior is analyzed to rigorously identify and measure behaviors that differ between wildtype and ASD model mice.

Datta’s team is currently using these approaches to assess behavior in three different mouse models for autism — SHANK3, CNTNAP2, and 16p11.2 deletion mice — and to characterize the behavioral impact of treatment with several potential therapeutic agents. Taken together, this proposal develops new technical approaches for studying behavior in ASD model mice, tests the role of ASD risk genes in behavior, and measures the ability of potential therapeutic agents to correct behavioral abnormalities apparent in ASD model mice.



1.Wiltschko A.B., et al. Neuron 88, 1121-1135 (2015) PubMed
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