Overview of Mouse Models of Autism Spectrum Disorders

Abstract

This overview covers many well-characterized mouse models of autism spectrum disorders (ASDs). As there are numerous mouse models of varying design and description in the literature, the models presented here represent examples of genetically engineered models where human genetic evidence supports a causative relationship between the targeted mutation and the behavioral phenotype of the mouse models. As the diagnosis of ASDs is primarily based on behavioral evaluations in humans, we highlight the murine behavioral analogs to human autistic behaviors in different models. However, because the characteristic behaviors of ASDs in humans are in the domains of social interaction, communication, and restricted interests, the translational value of various behavioral assays used in rodents remains a subject of debate. Using genetically engineered mouse models with good construct and face validity will provide a platform for investigating underlying pathophysiological mechanisms and discovering potential therapeutic interventions which will hopefully translate into effective treatments for ASDs. We also illustrate several significant challenges in the field of modeling ASDs in rodents due to the considerable clinical and molecular heterogeneity associated with ASDs in humans.

Enhanced Neuronal Activity in the Medial Prefrontal Cortex during Social Approach Behavior

“…Mouse models of social dysfunction are widely used to investigate neural mechanisms underlying various neuropsychiatric diseases, such as autism spectrum disorders (ASDs), depression, and schizophrenia (Bey and Jiang, 2001;Yang et al, 2011;Ting et al, 2012;Kleijer et al, 2014;Lombardi et al, 2015;Kazdoba et al, 2016). Previous studies have found that the medial prefrontal cortex (mPFC) plays a crucial role in mouse social behavior.…”

Monogenic mouse models of autism spectrum disorders: Common mechanisms and missing links

“…Nevertheless, careful review of common findings in these models contributes to a basic understanding of the pathophysiology contributing to autistic behaviors. The behavioral phenotypes in some of these ASD models have recently been reviewed in a separate paper (Bey and Jiang, 2014), so this review will focus on biochemical, cellular, and synaptic findings from select mouse models of ASDs induced by a mutation in a single gene. It should be noted that there are many models that we excluded, including inbred strains, chromosomal CNVs, and environmentally induced models, due to limited space and the fact that the biological mechanisms in these models are currently less understood.…”

“…However, heterozygous mice ( Tsc1 +/− or Tsc2 +/− ) from these constructs recapitulate many of the phenotypes of TSC observed in humans, including ASD-like behaviors (reviewed in Bey and Jiang, 2014). …”

Synapse alterations in autism: Review of animal model findings

“…Mutations in neurexins, neuroligins and Shank genes might have impact on the development of complex behaviors. Neuroligin 1 mutant mice targeting the first two coding exons displayed a mild ASD-related phenotype 56 . They showed increased repetitive, stereotyped grooming behavior.…”

“…Neuroligin 3 mutant mice, targeting exons 2-3 displayed behavioral phenotype reminiscent of the lead symptoms of ASD (ref. 56 ). These mice displayed reduced ultrasonic vocalization and a lack of social novelty preference.…”