New Shank3 Mouse Models

A number of Shank3 mouse models have been created in an effort to explain the role that Shank3 mutations play in the development of autism spectrum disorder (ASD) features. Following the characterization of the first Shank3 mouse by Dr. Ozlem Bozdagi Gunal and her team at Mount Sinai (See previous post: New mouse model for Phelan-McDermid Syndrome), three more groups have described results with mice that examine Shank3 function.

Peça et al generated two different mouse models, referred to as Shank3a and Shank3b. They targeted different areas of the gene sequence and showed that mice lacking both Shank3a and Shank3b copies develop autistic-like behaviors, such as social interaction deficits, increased anxiety and excessive grooming.

Wang et al used a strategy similar to the one followed by Dr. Bozdagi Gunal and her team in order to create mice missing full length Shank3 (Shank3a). Dr. Wang’s team found that a loss of both copies results in social and cognitive deficits, repetitive behaviors and impairments in synaptic plasticity. Behavioral tests showed that complete loss of Shank3a led to impairments in social approach and affiliation, communication deficits, learning difficulties, obsessive behaviors and mild motor abnormalities. The team also explored the functional consequences of Shank3 loss and found that nerve cell communication in the hippocampus, a brain structure that plays an important role in learning and memory functions, was impaired.

Using a different approach Bangash et al, created a different Shank3 mouse, which results in the deletion of a section of the Shank3 protein, referred to as Shank3+/ΔC. A decrease in Shank3 levels resulted in a phenotype that included deficits in social approach and communication but left cognitive processes such as learning and memory relatively intact.

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A number of Shank3 mouse models have been created in an effort to explain the role that Shank3 mutations play in the development of autism spectrum disorder (ASD) features. Following the characterization of the first Shank3 mouse by Dr. Ozlem Bozdagi Gunal and her team at Mount Sinai (See previous post: ), three more groups have described results with mice that examine Shank3 function.

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