Characterizing vulnerable brain areas and circuits in mouse models of autism: Towards understanding pathogenesis and new therapeutic approaches.

Neurosci Biobehav Rev 2018 Nov 21. Epub 2018 Nov 21.

Medical Innovation Center Kyoto University Graduate School of Medicine, Japan. Electronic address:

Recent human genetics studies have identified many genetic variants that may be responsible for autism spectrum disorder (ASD). ASD mouse models with genetic modifications mimicking these rare genetic variants have provided invaluable mechanistic insights into the disruption of various biological processes and brain areas/circuitry affected in ASD patients. In this review, we begin by reviewing several mouse models for ASD-associated copy number variations (CNVs) to illustrate how they have been employed to establish causal links between their behavioral phenotypes and the affected genes. We then focus on studies using one of the principal behavioral abnormalities associated with ASD, social behavior, to identify the molecular and circuit-level deficits involved. Finally, we end by discussing other mouse models designed to probe how the disruption of specific biological processes such as autophagy and neurogenesis may contribute to ASD pathogenesis. By achieving a greater understanding of the pathophysiology and pathogenic mechanisms involved in ASD and related disorders, novel therapeutic strategies may be devised for ASD patients in the near future.

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http://dx.doi.org/10.1016/j.neubiorev.2018.08.001DOI Listing
November 2018

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