Cited by 541Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroendocrine regulation and behavior

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Mouse Behavioral Assays Relevant to the Symptoms of Autism*

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Crawley, Jacqueline N.·2007·Brain Pathology

DOI 10.1111/j.1750-3639.2007.00096.xPMC PMC8095652

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Abstract

While the cause of autism remains unknown, the high concordance between monozygotic twins supports a strong genetic component. The importance of genetic factors in autism encourages the development of mutant mouse models, to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (i) face validity (resemblance to the human symptoms) (ii) construct validity (similarity to the underlying causes of the disease) and (iii) predictive validity (expected responses to treatments that are effective in the human disease). There is a growing need for mouse behavioral tasks with all three types of validity, to define robust phenotypes in mouse models of autism. Ideal mouse models will incorporate analogies to the three diagnostic symptoms of autism: abnormal social interactions, deficits in communication and high levels of repetitive behaviors. Social approach is tested in an automated three chambered apparatus that offers the subject a choice between spending time with another mouse, with a novel object, or remaining in an empty familiar environment. Reciprocal social interaction is scored from videotapes of interactions between pairs of unfamiliar mice. Communication is evaluated by measuring emission and responses to vocalizations and olfactory cues. Repetitive behaviors are scored for measures of grooming, jumping, or stereotyped sniffing of one location or object. Insistence on sameness is modeled by scoring a change in habit, for example, reversal of the spatial location of a reinforcer in the Morris water maze or T‐maze. Associated features of autism, for example, mouse phenotypes relevant to anxiety, seizures, sleep disturbances and sensory hypersensitivity, may be useful to include in a mouse model that meets some of the core diagnostic criteria. Applications of these assays include (i) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism; (ii) characterization of inbred strains of mice; (iii) evaluation of environmental toxins; (iv) comparison of behavioral phenotypes with genetic factors, such as unusual expression patterns of genes or unusual single nucleotide polymorphisms; and (v) evaluation of proposed therapeutics for the treatment of autism.

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10.1002/1096-8628(20010108)105:1<53::AID-AJMG1059>3.0.CO;2-U · DOI

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Behavioural phenotyping assays for mouse models of autism
Silverman, J. L., Yang, M., Lord, C., & Crawley, J. N. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2851 · Cited by 1,462
“One compelling approach to test hypotheses about the many candidate genes for autism is to generate analogous mutations in the mouse genome and evaluate the mutant line for phenotypes analogous to the symptoms of autis”
BackgroundSelf-citation
Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior
Zhan, Y., Paolicelli, R. C., Sforazzini, F., Weinhard, L., Bolasco, G., Pagani, F., Vyssotski, A. L., Bifone, A., Gozzi, A., Ragozzino, D., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3641 · Cited by 1,236
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“Cntnap2 / Mice Show Communication and Social Behavior Abnormalities Isolation-induced ultrasonic vocalizations (UsVs) are distress calls emitted by pups when separated from their mother, representing an infant-mother vocal communicative behavior that is thought to be relevant to ASD (Crawley, 2007; Silverman et al., 2…”
Microbiota is essential for social development in the mouse
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Crespi, B. J., & Badcock, C. R. (2008) · Behavioral and Brain Sciences · doi:10.1017/s0140525x08004214 · Cited by 635
“Various animal models of autism are being similarly explored (Crawley 2007; Moy et al. 2007).”
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Authors: Crawley, J. N.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Crawley, Jacqueline N.
ORCID: Crawley, Jacqueline N.
Venue: Brain Pathology
Publisher: Wiley
Published: 2007-10
Volume: 17
Issue: 4
Pages: 448-459
ISSN: 1015-6305 (ISSN-L)
1750-3639
DOI: 10.1111/j.1750-3639.2007.00096.x
PMC: PMC8095652
OpenAlex: W2076566560
Cited by: 541
References: 216
Citations by year: 2026: 10 · 2025: 18 · 2024: 18 · 2023: 24 · 2022: 25 · 2021: 31 · 2020: 33 · 2019: 34 · 2018: 21 · 2017: 28 · 2016: 30 · 2015: 38 · 2014: 30 · 2013: 41 · 2012: 42
FWCI: 1.68
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 3 d)
Locations: Brain Pathology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5u54mh066418-05)
U.S. Public Health Service (NICHD P30)
National Institute of Mental Health (U54-MH066418, MH66418)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Keywords: autism spectrum disorder, mouse models of autism, behavioral assays, social interaction, communication difficulties, repetitive behavior, insistence on sameness, reciprocal social interaction, vocalizations, olfactory cues, grooming, anxiety, seizures, sleep disorders, sensory hypersensitivity, phenotyping, inbred mouse strains, environmental toxins
MeSH terms: Animals, Autistic Disorder, Behavior, Animal, Biological Assay, Disease Models, Animal, Humans, Mice, Transgenic, Phenotype, Social Behavior Disorders, Genetic Predisposition to Disease, Mice

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