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Mouse Behavioral Assays Relevant to the Symptoms of Autism*
Open accessAbstract
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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“Because impairments in social behavior is one of hallmarks of ASD1415”
From Transient blockade of ERK phosphorylation in the critical period causes autistic phenotypes as an adult in mice (2015) · cites this paper as [15]
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Items 301–400 of 538
Haddad, F. L., Oliveira, C. D., & Schmid, S. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1160243 · Cited by 22
“Each rat’s preference for a conspecific over an inanimate object (sociability), as well as its preference for a stranger rat over a familiar rat (social novelty), were assessed using the previously established 3-chamber assay (Moy et al., 2004; Crawley, 2007; Scott et al., 2020).”
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“…of these grooming datawith othermouse behaviors using the MPD online tools has revealed correlations with anxiety-sensitive behaviors, reflecting the rapidly recognized importance of measuring grooming in animal anxiety paradigms (Crawley, 2007; Hart et al., 2010; Kalueff and Tuohimaa, 2005b).”
Takechi, K., Suemaru, K., Kiyoi, T., Tanaka, A., & Araki, H. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.02.021 · Cited by 21
“A three-chamber social test was used to evaluate autistic-like behavior (Crawley, 2007).”
Social Isolation Alters Social and Mating Behavior in the R451C Neuroligin Mouse Model of Autism
Burrows, E. L., Eastwood, A. F., May, C., Kolbe, S., Hill, T., McLachlan, N. M., Churilov, L. P., & Hannan, A. J. (2017) · Neural Plasticity · doi:10.1155/2017/8361290 · Cited by 20
“Aberrant reciprocal social interactions can be probed in mouse models using assays that measure tendency to spend time with an unfamiliar mouse [20, 23].”
Onakomaiya, M. M., Porter, D. M., Oberlander, J. G., & Henderson, L. (2014) · Hormones and Behavior · doi:10.1016/j.yhbeh.2014.04.008 · Cited by 20
“Tests for social interactions have been assessed in mice by using a social choice paradigm, wherein diminished exploration of the novel mouse may reflect an anxiety-related state (Crawley, 2007).”
MethodmTOR-Dependent Spine Dynamics in Autism
Chaudry, S., & Vasudevan, N. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.877609 · Cited by 23
“…tasks such as the social discrimination and social interaction tasks and the marble burying task that mimic the ASC phenotype are well established (Crawley, 1999, 2007), focusing on genes that affect spine density or spine morphology in rodents may lead to mechanistic insight (Lazaro and…”
BackgroundCastelhano, A. S. S., Ramos, F. O., Scorza, F. A., & Cysneiros, R. M. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1291-2 · Cited by 20
Genetic loss of diazepam binding inhibitor in mice impairs social interest
Ujjainwala, A. L., Courtney, C. D., Rhoads, S., Rhodes, J. S., & Christian, C. A. (2017) · Genes Brain & Behavior · doi:10.1111/gbb.12442 · Cited by 22
“An increase in the amount of repetitive self-grooming is commonly used as a parameter of autistic-like behavior in mice.(67,68) Presently, it is unclear whether the increase in repetitive grooming seen in DBI mice reflects autistic-like stereotyped behavior or if it is largely a byproduct of the skin and fur phenotype…”
BackgroundLópez‐Aranda, M. F., Chattopadhyay, I., Boxx, G. M., Fraley, E., Silva, T. K., Zhou, M., Phan, M., Herrera, I., Taloma, S. E., Mandanas, R., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf2073 · Cited by 19
“Disruption of USV calling patterns is thought to model communication deficits in ASD (46, 49).”
BackgroundRegulation of Adult Neurogenesis by the Fragile X Family of RNA Binding Proteins
Patzlaff, N. E., Shen, M., & Zhao, X. (2017) · Brain Plasticity · doi:10.3233/bpl-170061 · Cited by 18
“A common impairment in autism and FXS is intellectual disability, which can be modeled in mouse models of learning and memory [209].”
BackgroundPrkn knockout mice show autistic-like behaviors and aberrant synapse formation
Huo, Y., Lü, W., Tian, Y., Hou, Q., & Man, H. (2022) · iScience · doi:10.1016/j.isci.2022.104573 · Cited by 19
“Therefore, we performed three-chamber tests to assess their sociability and interest in social novelty (Crawley, 2007) (Figure 1B).”
MethodNew Perspectives on Rodent Models of Advanced Paternal Age: Relevance to Autism
Foldi, C. J., Eyles, D. W., Flatscher‐Bader, T., McGrath, J. J., & Burne, T. H. J. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00032 · Cited by 20
“Therefore, ASD may be particularly difficult to model in rodents (Crawley, 2007).”
BackgroundLetting a Typical Mouse Judge Whether Mouse Social Interactions Are Atypical
Shah, C. R., Forsberg, C. G., Kang, J., & Veenstra-VanderWeele, J. M. (2013) · Autism Research · doi:10.1002/aur.1280 · Cited by 18
“A number of assays have been developed to evaluate the social behavior of mouse models of autism susceptibility [Bolivar, Walters, & Phoenix, 2007; Crawley, 2007; Moy & Nadler, 2008; Moy et al., 2004; Panksepp & Lahvis, 2007; Pobbe et al., 2010; Roullet, Wohr, & Crawley, 2010; Silverman et…”
BackgroundSocial interaction test: a sensitive method for examining autism-related behavioral deficits
Ikeda, K., Sato, A., Mizuguchi, M., & Ikeda, K. (2013) · Protocol Exchange · doi:10.1038/protex.2013.046 · Cited by 17
Anacker, A. M. J., Moran, J., Santarelli, S., Forsberg, C. G., Rogers, T. D., Stanwood, G. D., Hall, B. J., Delpire, E. J., Veenstra-VanderWeele, J. M., & Saxe, M. (2019) · Autism Research · doi:10.1002/aur.2098 · Cited by 17
“advantage of being near the P35–P45 age of the subjects used for electrophysiology while also being during the stage at which the conducted tests are typically done, for comparison with other studies [Crawley, 2007].”
BackgroundResultInfluentialUnderstanding the circuit basis of cognitive functions using mouse models
Nakajima, M., & Schmitt, L. I. (2019) · Neuroscience Research · doi:10.1016/j.neures.2019.12.009 · Cited by 19
Blumkin, E., Levav-Rabkin, T., Melamed, O. C., Galron, D., & Golan, H. M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.52 · Cited by 19
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Thapar, A., & Rutter, M. L. (2015) · Wiley eBooks · doi:10.1002/9781118381953.ch12 · Cited by 18
Sociability development in mice with cell-specific deletion of the NMDA receptor NR1 subunit gene
Ferri, S. L., Pallathra, A. A., Kim, H., Dow, H. C., Raje, P., McMullen, M., Bilker, W. B., Siegel, S. J., Abel, T., & Brodkin, E. S. (2020) · Genes, Brain and Behavior · doi:10.1111/gbb.12624 · Cited by 15
“more likely due to variability in social behavior across experiments, which is observable in a number of social approach studies.(88,89,108,109)”
BackgroundReddy, D., Li, Y.-F., Qamari, T., & Ramakrishnan, S. (2024) · Current Protocols · doi:10.1002/cpz1.70019 · Cited by 16
Multidimensional nature of dominant behavior: Insights from behavioral neuroscience
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Harda, Z., Chrószcz, M., Misiołek, K., Klimczak, M., Szumiec, Ł., Kaczmarczyk-Jarosz, M., & Parkitna, J. M. R. (2022) · Scientific Reports · doi:10.1038/s41598-022-15427-9 · Cited by 16
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Endophenotype trait domains for advancing gene discovery in autism spectrum disorder
Mosconi, M. W., Stevens, C. J., Unruh, K. E., Shafer, R. L., & Elison, J. T. (2023) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-023-09511-y · Cited by 16
“Multiple mouse models of autism have documented reduced social approach relative to wild-type (WT) mice, suggesting multiple gene variants associated with ASD may contribute directly to diminished interest in or increased resistance to social interaction [140, 141].”
BackgroundBrain Serotonin Signaling Does Not Determine Sexual Preference in Male Mice
Angoa‐Pérez, M., Herrera‐Mundo, N., Kane, M. J., Sykes, C. E., Anneken, J. H., Francescutti, D. M., & Kuhn, D. M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118603 · Cited by 17
“, intruder mice interacting with each other as well as with the resident mouse), we modified the test to restrict access of the resident mouse with the intruder mice by placing the intruders in wire cups as used in the three chamber social approach test in the study of autism-like behaviors in rodents [40,44,45].”
MethodSex‐dependent influence of postweaning environmental enrichment in Angelman syndrome model mice
Cosgrove, J. A., Kelly, L. K., Kiffmeyer, E. A., & Kloth, A. D. (2022) · Brain and Behavior · doi:10.1002/brb3.2468 · Cited by 16
“…anxiety-related behaviors from confounding motor deficits in ASmice, including the elevated-plusmaze (Born et al., 2017; Ciarlone et al., 2016, 2017; Dutta & Crawley, 2020), the lightdark task (Dutta & Crawley, 2020; Godavarthi et al., 2012; Jiang et al., 2010), or other tasks (Crawley, 2007).”
BackgroundAssociation between sociability and diffusion tensor imaging in BALB/cJ mice
Kim, S., Pickup, S., Fairless, A. H., Ittyerah, R., Dow, H. C., Abel, T. G., Brodkin, E. S., & Poptani, H. (2011) · NMR in Biomedicine · doi:10.1002/nbm.1722 · Cited by 16
“heterogeneous set of human disorders that we commonly refer to as ASDs, brain structural and behavioral endophenotypes relevant to ASDs can be studied experimentally in mice for the purposes of testing hypotheses about brain–behavior relationships (18).”
BackgroundObservational fear learning in degus is correlated with temporal vocalization patterns
Lidhar, N. K., Insel, N., Dong, J. Y., & Takehara‐Nishiuchi, K. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.06.011 · Cited by 17
Javaheri, E. S. S. J., Bigdeli, M. R., Zibaii, M. I., Dargahi, L., & Pouretemad, H. R. (2019) · NeuroMolecular Medicine · doi:10.1007/s12017-019-08526-w · Cited by 15
“One day after completing optogenetic stimulation period, in PND 80, adult rats were subject to estimation of repetitive behavior and stranger phobia as autistic-like behavior (Crawley 2007, 2012).”
MethodPrenatal Nutritional Intervention Reduces Autistic-Like Behavior Rates Among Mthfr-Deficient Mice
Orenbuch, A., Fortis, K., Taesuwan, S., Yaffe, R., Caudill, M. A., & Golan, H. M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00383 · Cited by 16
“…of the number of entries by the tested mouse into the chambers, the total duration of time it spent in each chamber, the time the tested mouse spent sniffing Stranger 1 and Stranger 2 and its movement parameters were taken on both days (Nadler et al., 2004; Crawley, 2007; Kezurer et al., 2013).”
MethodDaini, E., Hagmeyer, S., Benedictis, C. A. D., Cristóvão, J. S., Bodria, M., Ross, A. M., Raab, A., Boeckers, T. M., Feldmann, J., Gomes, C. M., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01694-z · Cited by 19
Korade, Ž., Folkes, O. M., & Harrison, F. E. (2013) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.03.007 · Cited by 16
Sadigurschi, N., & Golan, H. M. (2018) · Genes Brain & Behavior · doi:10.1111/gbb.12547 · Cited by 16
“To assess maternal and offspring Mthfr+/− genotype involvement in ASD-like phenotypes in adult mice, we applied a set of behavioral tests that were previously validated as measures of the core symptom domains of autism.(54,55) SADIGURSCHI AND GOLAN 5 of 17”
MethodPeleh, T., Ike, K. G. O., Frentz, I., Buwalda, B., de Boer, S. F., Hengerer, B., & Kas, M. J. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.04.045 · Cited by 15
“95 biological mechanism of symptoms independent of diagnosis (Cuthbert and Insel, 2010, 2013).”
BackgroundJagadeeswaran, I., Pruitt, A., Gautier, N. M., Crane, K., & Glasscock, E. (2021) · Brain and Behavior · doi:10.1002/brb3.2041 · Cited by 12
“…plexiglass three-chamber box (66-cm length × 45-cm width × 22-cm height), composed of a middle chamber separated by dividing walls with retractable doorways from two flanking and equalsized side chambers (20-cm length × 45-cm width), as previously described (Crawley, 2007; Moy et al., 2004).”
MethodAutism Spectrum Disorder: The Cerebellum, Genes, and Pathways
D’Mello, S. R. (2025) · Neurology International · doi:10.3390/neurolint17100173 · Cited by 15
“Similarly, mice lacking CNTNAP2 display reduced cerebellar volume [284].”
Naghizadeh, M., Mohajerani, M. H., & Whishaw, I. Q. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112732 · Cited by 19
Differential effects by sex with Kmt5b loss
Wickramasekara, R. N., Robertson, B., Hulen, J., Hallgren, J., & Stessman, H. A. F. (2021) · Autism Research · doi:10.1002/aur.2516 · Cited by 15
“A minimum of nine animals per genotype and sex were used for all experiments based on similar previous studies (Crawley, 2007).”
MethodFertan, E., Wong, A. A., Purdon, M. K., Weaver, I. C. G., & Brown, R. E. (2020) · Genes Brain & Behavior · doi:10.1111/gbb.12696 · Cited by 16
“The behavioral deficits of MDGA2 mutant mice include increased repetitive jumping, reduced social contact with a novel mouse, reduced social investigation and impaired memory performance.59-62 Mutant and transgenic mouse models of ASD are engineered using different background strains (JAX SFARI website) and these back…”
BackgroundInfluentialYau, S., Yip, Y. S. L., Formolo, D. A., He, S., Lee, T. H.-Y., Wen, C., & Hryciw, D. H. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113538 · Cited by 14
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“Z, M Contextual and cued fear conditioning test (Hall and Suboski, 1995a; LeDoux, 2000; Fanselow and Poulos, 2005; Yu et al., 2006; Crawley, 2007)”
BackgroundInfluentialEffect of diazepam on sociability of rats submitted to neonatal seizures
Leite, I. S., Castelhano, A. S. S., & Cysneiros, R. M. (2016) · Data in Brief · doi:10.1016/j.dib.2016.03.029 · Cited by 14
Vasopressin as Possible Treatment Option in Autism Spectrum Disorder
László, K., Vörös, D., Correia, P., Fazekas, C. L., Török, B., Plangár, I., & Zelena, D. (2023) · Biomedicines · doi:10.3390/biomedicines11102603 · Cited by 13
“According to our current knowledge, the common ancestral gene (along with their receptors [83]) went through duplication, and, over the course of the vertebrate evolution, the VP and OT genes gained their tail-to-tail orientation [84–86].”
BackgroundGawlińska, K., Gawliński, D., Kowal-Wiśniewska, E., Jarmuż‐Szymczak, M., & Filip, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189662 · Cited by 13
“We also confirmed the increase in repetitive behavior in the offspring from the HFD group by assessing self-grooming, a parameter that is commonly used in the assessment of autistic-like behavior in rodents [34,35].”
BackgroundThe translational genetics of ADHD and related phenotypes in model organisms
Cabana‐Domínguez, J., Antón-Galindo, E., Fernàndez‐Castillo, N., Singgih, E. L., O’Leary, A., Norton, W., Strekalova, T. V., Schenck, A., Reif, A., Lesch, K., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104949 · Cited by 15
“On the other hand, the rewarding effects of drugs can also be studied using conditioned behaviors like conditioned place preference (CPP) or drug self-administration (Table 1 and Supplementary Table S1).”
MethodInfluentialHunsaker, M. R. (2012) · Behavioral Neuroscience · doi:10.1037/a0028453 · Cited by 14
“As a rule of thumb, it is best to perform at most a set of experiments evaluating basic sensory function in mice (cf., Crawley, 2007), followed by tasks evaluating each attribute in turn, followed potentially by the water maze/avoidance tasks and fear conditioning as the final task to prevent…”
BackgroundMethodOlexová, L., Talarovičová, A., Lewis-Evans, B., Borbélyová, V., & Kršková, L. (2012) · Neuroscience Research · doi:10.1016/j.neures.2012.10.004 · Cited by 13
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Wada, M., Ide, M., Atsumi, T., Sano, Y., Shinoda, Y., Furuichi, T., & Kansaku, K. (2019) · Scientific Reports · doi:10.1038/s41598-019-43996-9 · Cited by 13
Cardiac Dysfunction in a Mouse Vascular Dementia Model of Bilateral Common Carotid Artery Stenosis
An, L., Chopp, M., Zacharek, A., Shen, Y., Chen, Z., Yu, Q., Li, W., Landschoot‐Ward, J., Liu, Z., & Venkat, P. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.681572 · Cited by 13
Zilkha, N., Chuartzman, S. G., Fishman, R., Ben‐Dor, S., & Kimchi, T. (2024) · Scientific Reports · doi:10.1038/s41598-024-70062-w · Cited by 14
“Time spent in each chamber was scored using the Ethovision software (Noldus) and used to examine ASD-related reduced sociability 41 .”
BackgroundMethodInfluentialLeung, B. K., Merlin, S., Walker, A. K., Lawther, A. J., Paxinos, G., Eapen, V., Clarke, R. A., Balleine, B. W., & Furlong, T. M. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114610 · Cited by 11
“However, whilst both groups of mice displayed specific PIT, there was an increased capacity for the auditory stimuli previously paired with food to promote instrumental responding for food, as KD mice increased lever responses during both the same and different CSs compared to WT mice (Experiment 1).”
InfluentialAutistic childrens: A neuroimmune perspective
Dantzer, R., & Kelley, K. W. (2008) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2008.03.001 · Cited by 12
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Ma, L., Kulesskaya, N., Võikar, V., & Tian, L. (2015) · Psychiatry Research · doi:10.1016/j.psychres.2015.01.001 · Cited by 12
“Modified resident–intruder test This test is modified from the classical resident–intruder test performed in home cage (Crawley, 2007).”
Social behavior impairment in offspring exposed to maternal seizures in utero
Novaes, G. F., Amado, D., Scorza, F. A., & Cysneiros, R. M. (2012) · Journal of Neural Transmission · doi:10.1007/s00702-011-0751-1 · Cited by 12
“(1983), do Vale et al. (2010) investigated the effect of epileptic seizures during pregnancy on the hippocampal expression of calcium-binding proteins in the offspring. In brief, the authors showed a change in specific neuronal subpopulations; that is, the number of calbindinpositive interneurons was lower, and the nu…”
BackgroundMethodResultInfluentialOlfactory classical conditioning in neonatal mouse pups using thermal stimuli
Bollen, B., Matrot, B., Ramanantsoa, N., den Bergh, O. V., D’Hooge, R., & Gallego, J. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.12.030 · Cited by 12
From rodents to humans: Rodent behavioral paradigms for social behavioral disorders
Guo, M., & Sun, L. (2023) · Brain Circulation · doi:10.4103/bc.bc_48_23 · Cited by 11
“…exhibit behavioral deficits similar to the symptoms of psychiatric disorders in humans, including problems with social interaction, repetitive behaviors, lack of interest, etc. [13] However, social interactions in humans are extremely complex, highly dynamic, emotional, and experience based.”
BackgroundSocial Deficits and Cerebellar Degeneration in Purkinje Cell Scn8a Knockout Mice
Yang, X., Yin, H., Wang, X., Sun, Y., Bian, X., Zhang, G., Li, A., Cao, A., Li, B., Ebrahimi‐Fakhari, D., et al. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.822129 · Cited by 10
“Time spent interacting with the novel animal and with the object was recorded by an examiner with a stopwatch (Crawley, 2007).”
MethodCorredor, K., Duran, J. M., Herrera-Isaza, L., Forero, S., Quintanilla, J. P., Gomez, A., Martínez, G. S., & Cárdenas, F. P. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.837661 · Cited by 17
“It aims to quantify peer-directed behaviors, exploration of odor cues, ultrasonic vocalizations, and stereotypies (Crawley, 2007).”
BackgroundIncreased susceptibility to mild neonatal stress in MTHFR deficient mice
Kezurer, N., Galron, D., & Golan, H. M. (2013) · Behavioural Brain Research · doi:10.1016/j.bbr.2013.07.037 · Cited by 12
Williams, A. L., & DeSesso, J. M. (2014) · Critical Reviews in Toxicology · doi:10.3109/10408444.2014.907772 · Cited by 11
“CPF treatment had no reported eff ect on self-grooming behaviors in pups assessed on PND4 – PND12.”
BackgroundMethodInfluentialReduced sulfate plasma concentrations in the BTBR T+tf/J mouse model of autism
Corley, M. J., Meyza, K. Z., Blanchard, D. C., & Blanchard, R. J. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.04.010 · Cited by 11
“These criteria emphasize the need for relevant ASD animal models [4], leading to extensive effort in the development of autism-relevant behavioral tests and identification of candidate strains of mice that exhibit an ASD behavioral phenotype [5–9].”
BackgroundMouse Behavior and Models for Autism Spectrum Disorders
Ricceri, L., Michetti, C., & Scattoni, M. L. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800109-7.00017-0 · Cited by 13
Influence of Gut Microbiota on Behavior and Its Disturbances
Ignatova, V. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.85317 · Cited by 13
Mouse model systems of autism spectrum disorder: Replicability and informatics signature
Kabitzke, P., Morales, D. V., He, D., Cox, K., Sutphen, J. C., Thiede, L., Sabath, E. V., Hanania, T., Biemans, B., & Brunner, D. (2020) · Genes Brain & Behavior · doi:10.1111/gbb.12676 · Cited by 10
“Phenotypic analyses of model systems of ASD typically probe mouse functional domains putatively reflecting the core ASD triad, namely, social function, communication, and repetitive behaviors (Moy, Nadler et al. 2006, Crawley 2007, Happé and Ronald 2008, Silverman, Yang et al. 2010).”
BackgroundSocial deficits in BTBR T+ Itpr3tf/J mice vary with ecological validity of the test
Winiarski, M., Kondrakiewicz, L., Kondrakiewicz, K., Jędrzejewska‐Szmek, J., Turzyński, K., Knapska, E., & Meyza, K. Z. (2022) · Genes Brain & Behavior · doi:10.1111/gbb.12814 · Cited by 9
“Enriched environment—mice previously housed for 2 weeks in the Intellicage system (TSE, DE) but did not undergo habituation to either transportation or the Experimenter.”
BackgroundInfluentialThe potential involvement of cholinergic system in finasteride induced cognitive dysfunction
Ahire, A., Nair, K. P., Rao, B. S. S., & Srikumar, B. N. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.105066 · Cited by 10
microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model
Woo, T., King, C., Ahmed, N. I., Cordes, M., Nistala, S., Will, M. J., Bloomer, C., Kibiryeva, N., Rivera, R. M., Talebizadeh, Z., et al. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13091412 · Cited by 12
“Those from control conditions have been routinely shown to spend significantly more time investigating the novel stranger as opposed to spending their time with the previous, familiar mouse [41,46].”
BackgroundMethodThe Evolving Landscape of Functional Models of Autism Spectrum Disorder
Ranjan, J., & Bhattacharya, A. (2025) · Cells · doi:10.3390/cells14120908 · Cited by 10
“When choosing a particular model, researchers should ensure it meets both construct validity (i.e., it faithfully recapitulates the underlying genetic or environmental cause, such as a patient mutation) as well as face validity (close similarity to the human clinical phenotype) [171,175].”
Martin‐Kenny, N., & Bérubé, N. G. (2020) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-020-09319-0 · Cited by 12
Bagosi, Z., Megyesi, K., Ayman, J., Rudersdorf, H., Ayaz, M. K., & Csabafi, K. (2023) · Biomedicines · doi:10.3390/biomedicines11082217 · Cited by 10
Li, X., Yennawar, M., Wiest, A., O’Brien, W. T., Babrowicz, B. M., White, R. S., Talos, D. M., & Jensen, F. E. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16350 · Cited by 11
“The procedure was performed in a three-chambered, rectangular arena consisting of a central chamber and two end chambers, as previously described (Crawley, 2007; Moy et al., 2007).”
MethodKelliher, K. R., & Munger, S. D. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00262 · Cited by 10
“…D. Munger, Department of Pharmacology and Therapeutics, University of Florida, PO Box 100267, Gainesville, FL 32610, USA steven.munger@ufl.edu Specialty section: This article was submitted to Systems Biology, a section of the journal Frontiers in Neuroscience Received: 16…”
BackgroundMethodIs it Safe to Use a Diuretic to Treat Seizures Early in Development ?
Ben‐Ari, Y., & Tyzio, R. (2011) · Epiliepsy currents/Epilepsy currents · doi:10.5698/1535-7511-11.6.192 · Cited by 10
Candidate Genes for Inherited Autism Susceptibility in the Lebanese Population
Kourtian, S., Soueid, J., Makhoul, N. J., Guisso, D. R., Chahrour, M. H., & Boustany, R. (2017) · Scientific Reports · doi:10.1038/srep45336 · Cited by 11
Wu, R., Jiang, X., Wu, X., Pang, J., Tang, Y., Ren, Z., Yang, F., Yang, S., & Wei, W. (2022) · Behavioural Processes · doi:10.1016/j.beproc.2022.104624 · Cited by 10
Domain interplay in mice and men: New possibilities for the “natural kinds” theory of emotion
Warnick, J. E., LaPorte, J. L., & Kalueff, A. V. (2010) · New Ideas in Psychology · doi:10.1016/j.newideapsych.2010.01.001 · Cited by 10
“1B) offers a novel way to carry out experiments that may provide a method of establishing animal model validity without necessitating emotions be natural kinds (Kalueff, Ren-Patterson, et al., 2008).”
BackgroundMethodStephen, I., Jessica, A., Maria, R., Amy, L., & Erin, E. (2011) · InTech eBooks · doi:10.5772/18613 · Cited by 9
“Impaired sociability is a domain of psychopathology that contributes significantly to the functional disability and poor quality of life of persons with Autism Spectrum Disorders (ASDs) (Brodkin, 2007; Crawley, 2004, 2007; Deutsch et al., 2011).”
BackgroundMethodMultisensory Stimulation Reverses Memory Impairment in Adrβ3KO Male Mice
Ravache, T. T., Batistuzzo, A., Nunes, G. G., Gomez, T. G. B., Lorena, F. B., do Nascimento, B. P. P., Bernardi, M. M., Lima, E. R. R., Martins, D. O., Campos, A. C. P., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310522 · Cited by 9
“The same measures were taken as for the social preference test [75,76].”
MethodHill‐Yardin, E. L., & Hannan, A. J. (2013) · Behavioral Neuroscience · doi:10.1037/a0033319 · Cited by 9
“Sensorimotor function in rodent models is assessed using a range of standard assays (Crawley, 2007), and data are now emerging for some of these animal models of ASD.”
Anxiolytic-like effect of the leaves of Pseudospondias microcarpa (A. Rich.) Engl. in mice
Adongo, D. W., Mante, P. K., Kukuia, K. K. E., Ameyaw, E. O., Woode, E., & Azi, I. H. (2016) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2015-0067 · Cited by 9
Inactivation of the Catalytic Phosphatase Domain of PTPRT/RPTPρ Increases Social Interaction in Mice
Rajamani, K. T., O’Neill, B., Han, D. D., Frostholm, A., Rotter, A., & Gu, H. H. (2014) · Autism Research · doi:10.1002/aur.1390 · Cited by 9
“The three core diagnostic symptoms of ASD [impaired sociability, deficits in social communication and repetitive, and restrictive behaviors; American Psychiatric Association, 2013] have been modeled in animals [Crawley, 2007; Ricceri, Moles, & Crawley, 2007].”
BackgroundLamirault, C., Yu-Taeger, L., Doyère, V., Riess, O., Nguyen, H., & el Massioui, N. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.05.032 · Cited by 8
“…between new objects in one chamber and new conspecific (under a Plexiglas cylinder with multiple holes) in another chamber (Chabout et al., 2013; Crawley, 2007), our task ensures that animals exhibit normal preference for a social conspecific compared to other types of rewards (such as…”
BackgroundTreatment Approaches in Rodent Models for Autism Spectrum Disorder
Pietropaolo, S., Crusio, W. E., & D'Amato, F. R. (2015) · Current topics in behavioral neurosciences · doi:10.1007/7854_2015_433 · Cited by 9
Yang, Z., Zhao, Y., Li, Q., Shao, Y., Yu, X., Cong, W., Jia, X., Qu, W., Cheng, L., Xue, P., et al. (2019) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2019.03.006 · Cited by 8
JNK signaling provides a novel therapeutic target for Rett syndrome
Musi, C. A., Castaldo, A., Valsecchi, A. E., Cimini, S., Morello, N., Pizzo, R., Renieri, A., Meloni, I., Bonati, M. R., Giustetto, M., et al. (2021) · BMC Biology · doi:10.1186/s12915-021-01190-2 · Cited by 8
“The parameters analyzed as measures of spontaneous locomotor activity, exploratory activity, and state of anxiety were the duration of movements divided into the number of internal (the nine central squares) and external (the sixteen peripheral squares) square crossed, the time spent in the central and outer areas of…”
Empathy Study in Rodent Model of Autism Spectrum Disorders
Mony, T. J., Hong, M., & Lee, H. J. (2018) · Psychiatry Investigation · doi:10.30773/pi.2017.06.20 · Cited by 9
Neurodevelopmental and neuropsychiatric disorders affecting multisensory processes
Cascio, C. J., Simon, D. M., Bryant, L. K., DiCarlo, G. E., & Wallace, M. T. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-812492-5.00017-6 · Cited by 11
Neurobehavioral Alterations in a Genetic Murine Model of Feingold Syndrome 2
Fiori, E., Babicola, L., Andolina, D., Coassin, A., Pascucci, T., Patella, L., Han, Y.-C., Ventura, A., & Ventura, R. (2015) · Behavior Genetics · doi:10.1007/s10519-015-9724-8 · Cited by 9
Petrinovic, M. M., & Künnecke, B. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3200-z · Cited by 8
“A “phenotyping toolbox” consisting of numerous behavioural tests based on clinical observations has been developed in recent years in order to assess behavioural deficits in such rodent models of ASD (Crawley 2007;Moy et al. 2007, 2008; Scattoni et al. 2008; Silverman et al. 2010a).”
MethodA Systematic Review of the MDMA Model to Address Social Impairment in Autism
Chaliha, D. R., Mamo, J. C. L., Albrecht, M. A., Lam, V., Takechi, R., & Vaccarezza, M. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210101130258 · Cited by 7
“These are the ultrasonic-vocalisation test, the social-preference test, the social-novelty-preference test and the social-interaction test [71-73].”
MethodMatsumoto, Y., Miwa, H., Katayama, K., Watanabe, A., Yamada, K., Ito, T., Nakagawa, S., & Aruga, J. (2024) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2024.1386924 · Cited by 7
“…function may be associated with social behavior abnormalities in Slitrk4 KO mice because olfactory cues are essential for rodent social behaviors (Crawley, 2007; Ryan et al., 2008; Bourne et al., 2013), and enhanced fear memory and fear conditioning by foot shock impairs rodent social behaviors…”
BackgroundFrye, C. A., Cleveland, D. M., Sadarangani, A., & Torgersen, J. K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031173 · Cited by 7
O uso de ácido valproico para a indução de modelos animais de autismo: uma revisão
Schlickmann, E., & Fortunato, J. J. (2013) · Jornal Brasileiro de Psiquiatria · doi:10.1590/s0047-20852013000200009 · Cited by 7
Metadata
- Authors
- Crawley, J. N.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- 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
- 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
- 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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