The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
Autism‐like behavioral phenotypes in BTBR T+tf/J mice
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Repetitive behaviours are also often seen in autistic patients and in some mouse models of ASDs34–36.”
From Shank3 mutant mice display autistic-like behaviours and striatal dysfunction (2011) · cites this paper as [34]
In the citing paper
“In contrast to C57Bl6J mice, BTBR mice show no social preference in the test (Fig. 1c, d).20,21”
From Enhancement of anandamide-mediated endocannabinoid signaling corrects autism-related social impairment (2016) · cites this paper as [20]
In the citing paper
“BTBR T+tf/J (BTBR) is a commercially available inbred strain of mouse that displays behavioral phenotypes relevant to all three diagnostic symptoms of autism (60–62, 64, 66, 68–70, 72, 74–78).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [64]
In the citing paper
“Several naturally occurring inbred strains of mice display behavioral features that recapitulate diagnostic symptoms of neurodevelopmental disorders (59–70).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [64]
In the citing paper
“BTBR engages in low levels of reciprocal social interactions as juveniles and adults, minimal social approach by both males and females, and low levels of ultrasonic vocalizations in response to social olfactory cues and during reciprocal social interactions compared to other standard inbred strains such as C57BL/6J (B6) and FVB (60–62, 64, 66, 68–70, 74, 76–78).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [64]
In the citing paper
“Unlike mouse models based on identified genetic mutations, the background genes responsible for autism-relevant behavioral traits in these inbred strains of mice remain under investigation (64, 83–85).”
From Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism (2012) · cites this paper as [64]
In the citing paper
“The BTBR T+ Itpr3tf/J (BTBR) inbred mouse line exhibits the core ASD symptoms, including abnormal social behavior (McFarlane et al., 2008; Scattoni et al., 2008).”
From Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder (2019) · cites this paper as McFarlane et al., 2008
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
(1943) · The Nervous child · Cited by 8,870
Moy, S. S., Nadler, J. J., Perez, A., Barbaro, R. P., Johns, J. M., Magnuson, T. R., Piven, J., & Crawley, J. N. (2004) · Genes, Brain and Behavior · doi:10.1111/j.1601-1848.2004.00076.x · Cited by 1,522 · cited 4×
“Although previous experiments found similar social approach by subjects when the strangers were of the same or different strains, and of the same or different sex (Moy et al. 2004; Nadler et al. 2004), the present experiments used strangers of the same strain and sex for internal consistency.”
BackgroundResultInfluentialSelf-citationMuhle, R., Trentacoste, S. V., & Rapin, I. (2004) · Pediatrics · doi:10.1542/peds.113.5.e472 · Cited by 1,207
The neurobiology of attachment
Insel, T. R., & Young, L. J. (2001) · Nature Reviews Neuroscience · doi:10.1038/35053579 · Cited by 1,173
A Comparison of the Social Postures of Some Common Laboratory Rodents
Grant, E. C., & Mackintosh, J. H. (1963) · Behaviour · doi:10.1163/156853963x00185 · Cited by 1,167
Autism From 2 to 9 Years of Age
Lord, C., Risi, S., DiLavore, P. S., Shulman, C., Thurm, A., & Pickles, A. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.6.694 · Cited by 973 · cited 5×
“…presence of three defining symptoms: (1) aberrant reciprocal social interactions, (2) qualitative impairments in communication and (3) restricted repetitive and stereotyped patterns of behavior, interests and activities (DSM-IV 2000; Lord et al. 2001, 2006; Losh & Piven 2007; Volkmar et al. 2004).”
BackgroundInfluentialPten Regulates Neuronal Arborization and Social Interaction in Mice
Kwon, C.-H., Luikart, B. W., Powell, C. M., Zhou, J., Matheny, S. A., Zhang, W., Li, Y., Baker, S. J., & Parada, L. F. (2006) · Neuron · doi:10.1016/j.neuron.2006.03.023 · Cited by 970
Autism and the pervasive developmental disorders
Volkmar, F. R., & Klin, A. (2012) · doi:10.1093/med/9780199696758.003.0214 · Cited by 931
(2000) · Cited by 919
Self-citation
Research works printed but not linked: 1
- Bolivar V.J., 2003, Assessing autism‐like behaviors in inbred strains of mice, Soc Neurosci Abstr, 318, 13
Cited by
Sorted by citations
Items 801–817 of 817
Roussin, L. (2023) · theses.fr (ABES) · doi:10.70675/998d3bd1z4618z400dz998cz89e524b35aef · Cited by 1
Altérations sexe-dépendantes de la nociception dans un modèle d’autisme induit par le valproate
Glaunec, L. R. (2023) · theses.fr (ABES) · doi:10.70675/3d445796ze7caz426ezaafaza54d2130e2a3
Hippocampal APOE/S1P axis regulates synaptic and behavioral deficits in a mouse model of autism
Chen, X., (807797), Y. L., Song, X., Chen, J., Zhu, H., Sun, Q., Li, Z., Zhao, S., Zhang, C., & Wu, L. (2026) · Neurobiology of Disease · doi:10.1016/j.nbd.2026.107470
Kunevičius, A., Gawlińska, K., Burokas, A., & Gawliński, D. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03663-8
Gargus, J. J. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1883356
Zhang, N., Xue, L., Chai, S., Wang, T., Jiang, Y., Lei, J., & Wei, H. (2026) · Neuroscience · doi:10.1016/j.neuroscience.2026.07.034
Research on the role of gut microbiota metabolites in autism by multi-omics and network pharmacology
Hu, X., Zeng, Y., Li, J., Lin, Q., Liang, Z., Zhang, J., Jiang, M., Gao, S., & Liu, H. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1811435
Midzyanovskaya, I. S. (2026) · Exploration of neuroscience · doi:10.37349/en.2026.1006145
Czyrska, J., Poznański, P., Bernat, A., Winiarczyk, D., Ziętek, M. M., & Sampino, S. (2026) · Biology · doi:10.3390/biology15161425
Domain-specific and sex-dependent behavioral alterations in the BTBR mouse model of autism
Jackson, J., Houston, C., Cornils, M., Plummer, E., & Yu, C. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1932380
Estrada, K. B., Azamar, K. M. M., Wang, C., Sudi, S. D., Friday-Saunders, K., Márquez, V. S., Quintanilla‐Carvajal, M. X., Acosta‐González, A., Conde-Martínez, N., Porras, A. M., et al. (2026) · Journal of Functional Foods · doi:10.1016/j.jff.2026.107508 · Cited by 1
Goncalo, A. K. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261491809
Sikora, V., Bové, M., Agosti, L. P., Palmieri, R. P., Zafar, M., Tucci, P., Morgese, M. G., Schiavone, S., & Trabace, L. (2026) · British Journal of Pharmacology · doi:10.1111/bph.70693
Li, H., Li, Y., Liang, Z., Ji, Y., Lin, Y., Wang, X., Liu, S., Xiangyin, X., Zhang, Y., Tong, X., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-11180700/v1
Ivanov, M. N., Mladenov, A., Tsoneva, D. K., Napoli, A., Mazza, T., Tonchev, A. B., Coppola, I., Chiodi, V., Tartaglione, A. M., Vinciguerra, M., et al. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06277-x
Metadata
- 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.
- 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
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
