Behavioral phenotypes of genetic mouse models of autism

T. M. Kazdoba, P. T. Leach, Jacqueline Crawley

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

More than a hundred de novo single gene mutations and copy-number variants have been implicated in autism, each occurring in a small subset of cases. Mutant mouse models with syntenic mutations offer research tools to gain an understanding of the role of each gene in modulating biological and behavioral phenotypes relevant to autism. Knockout, knockin and transgenic mice incorporating risk gene mutations detected in autism spectrum disorder and comorbid neurodevelopmental disorders are now widely available. At present, autism spectrum disorder is diagnosed solely by behavioral criteria. We developed a constellation of mouse behavioral assays designed to maximize face validity to the types of social deficits and repetitive behaviors that are central to an autism diagnosis. Mouse behavioral assays for associated symptoms of autism, which include cognitive inflexibility, anxiety, hyperactivity, and unusual reactivity to sensory stimuli, are frequently included in the phenotypic analyses. Over the past 10 years, we and many other laboratories around the world have employed these and additional behavioral tests to phenotype a large number of mutant mouse models of autism. In this review, we highlight mouse models with mutations in genes that have been identified as risk genes for autism, which work through synaptic mechanisms and through the mTOR signaling pathway. Robust, replicated autism-relevant behavioral outcomes in a genetic mouse model lend credence to a causal role for specific gene contributions and downstream biological mechanisms in the etiology of autism.

Original languageEnglish (US)
Pages (from-to)7-26
Number of pages20
JournalGenes, Brain and Behavior
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Behavioral Genetics
Genetic Models
Autistic Disorder
Phenotype
Mutation
Genes
Gene Dosage
Reproducibility of Results
Knockout Mice
Transgenic Mice
Anxiety

Keywords

  • Anxiety-like
  • Autism
  • Cognition
  • Genes
  • Hyperactivity
  • Mice
  • Mutant models
  • Neurodevelopmental
  • Repetitive behavior
  • Sensory reactivity
  • Sociability
  • Social behavior
  • Vocalizations

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

Behavioral phenotypes of genetic mouse models of autism. / Kazdoba, T. M.; Leach, P. T.; Crawley, Jacqueline.

In: Genes, Brain and Behavior, Vol. 15, No. 1, 01.01.2016, p. 7-26.

Research output: Contribution to journalArticle

Kazdoba, T. M. ; Leach, P. T. ; Crawley, Jacqueline. / Behavioral phenotypes of genetic mouse models of autism. In: Genes, Brain and Behavior. 2016 ; Vol. 15, No. 1. pp. 7-26.
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