Cited by 817Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroendocrine regulation and behavior

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Autism‐like behavioral phenotypes in BTBR T+tf/J mice

McFarlane, H. G., Kusek, G. K., Yang, M., Phoenix, J. L., Bolivar, V. J., Crawley, J. N.·2008·Genes, Brain and Behavior

DOI 10.1111/j.1601-183x.2007.00330.x

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Abstract

Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Mouse models with face validity to the core symptoms offer an experimental approach to test hypotheses about the causes of autism and translational tools to evaluate potential treatments. We discovered that the inbred mouse strain BTBR T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three diagnostic symptoms of autism. BTBR displayed selectively reduced social approach, low reciprocal social interactions and impaired juvenile play, as compared with C57BL/6J (B6) controls. Impaired social transmission of food preference in BTBR suggests communication deficits. Repetitive behaviors appeared as high levels of self‐grooming by juvenile and adult BTBR mice. Comprehensive analyses of procedural abilities confirmed that social recognition and olfactory abilities were normal in BTBR, with no evidence for high anxiety‐like traits or motor impairments, supporting an interpretation of highly specific social deficits. Database comparisons between BTBR and B6 on 124 putative autism candidate genes showed several interesting single nucleotide polymorphisms (SNPs) in the BTBR genetic background, including a nonsynonymous coding region polymorphism in Kmo . The Kmo gene encodes kynurenine 3‐hydroxylase, an enzyme‐regulating metabolism of kynurenic acid, a glutamate antagonist with neuroprotective actions. Sequencing confirmed this coding SNP in Kmo , supporting further investigation into the contribution of this polymorphism to autism‐like behavioral phenotypes. Robust and selective social deficits, repetitive self‐grooming, genetic stability and commercial availability of the BTBR inbred strain encourage its use as a research tool to search for background genes relevant to the etiology of autism, and to explore therapeutics to treat the core symptoms.

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Authors: McFarlane, H. G., Kusek, G. K., Yang, M., Phoenix, J. L., Bolivar, V. J., & Crawley, J. N.
Affiliations: Kenyon College (US)
New York State Department of Health (US)
National Institute of Mental Health (US)
University of North Carolina at Chapel Hill (US)
Corresponding author: Crawley, J. N.
ORCID: Yang, M.
Bolivar, V. J.
Crawley, J. N.
Venue: Genes, Brain and Behavior
Publisher: Wiley
Published: 2007-04-27
Volume: 7
Issue: 2
Pages: 152-163
ISSN: 1601-183X (ISSN-L)
1601-1848
DOI: 10.1111/j.1601-183x.2007.00330.x
OpenAlex: W2071797996
Cited by: 812
References: 82
Citations by year: 2026: 23 · 2025: 36 · 2024: 41 · 2023: 49 · 2022: 52 · 2021: 62 · 2020: 51 · 2019: 44 · 2018: 47 · 2017: 48 · 2016: 63 · 2015: 50 · 2014: 52 · 2013: 42 · 2012: 51
FWCI: 8.99
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Genes Brain & Behavior (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute for Health and Care Research
National Institutes of Health
University of North Carolina at Chapel Hill
National Institute of Mental Health
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, BTBR T+tf/J mice, social dysfunction, social approach, reciprocal social interaction, social transmission of food preference, KMO, single nucleotide polymorphisms, autism candidate genes, inbred mouse strains, mouse models of autism
MeSH terms: Aging, Animals, Autistic Disorder, Circadian Rhythm, Disease Models, Animal, Food Preferences, Mice, Inbred C57BL, Mice, Inbred Strains, National Institute of Mental Health (U.S.), Phenotype, Play and Playthings, Social Behavior, United States, Videotape Recording, Mice

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Autism‐like behavioral phenotypes in BTBR T+tf/J mice

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