Comprehensive analysis of the 16p11.2 deletion and null Cntnap2 mouse models of autism spectrum disorder
Open accessAbstract
Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept1)4Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of therapeutics and we anticipate both our positive and negative findings will be utilized as a resource for the broader scientific community.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
16p11.2+/− models show reduced body size/weight, in contrast to the human obesity phenotype.
“However, 16p11.2+/− models show reduced body size/weight [4, 5, 60, 61, 63], in contrast to the human obesity phenotype.”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [61]
Hyperlocomotion is broadly reported in 16p11.2+/− mice, another behavioral feature that does not coincide directly with human symptomology.
“Hyperlocomotion is also broadly reported in 16p11.2+/− mice [4, 5, 59, 61, 63, 64, 70], another behavioral feature that does not coincide directly with human symptomology.”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [61]
All three lines of 16p11.2+/− mice display social deficits in various testing paradigms and an array of cognitive deficits.
“All 3 lines of 16p11.2+/− mice display social deficits in various testing paradigms [59–64], and an array of cognitive deficits [4, 59, 62–68].”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [61]
Mild motor deficits are present in 16p11.2+/− models, consistent with human phenotypes.
“Mild motor deficits are also present in these models [4, 61, 68], consistent with human phenotypes.”
From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [61]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
Strong association of de novo copy number mutations with autism
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., et al. (2007) · Science · doi:10.1126/science.1138659 · Cited by 2,795 · see citing works
Model of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768 · see citing works
McDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A. S., Zackai, E. H., Emanuel, B. S., Vermeesch, J. R., Morrow, B. E., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.71 · Cited by 2,236 · see citing works
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · cited 1× · see citing works
“An added difficulty arises in autism spectrum disorder (ASD) due to the enormous variety of genetic factors, with an estimated 230–400 autism susceptibility genes (even more, depending on the method of assessment [2–4]), in addition to environmental risk factors that are hypothesized to contribute to the behavioral ph…”
BackgroundDe novo mutations revealed by whole-exome sequencing are strongly associated with autism
Sanders, S. J., Murtha, M. T., Gupta, A. R., Murdoch, J. D., Raubeson, M. J., Willsey, A. J., Ercan-Sencicek, A. G., DiLullo, N. M., Parikshak, N. N., Stein, J. L., et al. (2012) · Nature · doi:10.1038/nature10945 · Cited by 2,084 · see citing works
Lord, C., Rutter, M., Goode, S., Heemsbergen, J., Jordan, H., Mawhood, L., & Schopler, E. (1989) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02211841 · Cited by 2,030 · see citing works
Structural Variation of Chromosomes in Autism Spectrum Disorder
Marshall, C. R., Noor, A., Vincent, J. B., Lionel, A. C., Feuk, L., Skaug, J., Shago, M., Moessner, R., Pinto, D., Ren, Y., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2007.12.009 · Cited by 1,815 · see citing works
Association between Microdeletion and Microduplication at 16p11.2 and Autism
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Saemundsen, E., Stefansson, H., Ferreira, M. A. R., Green, T., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa075974 · Cited by 1,666 · see citing works
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 1,545 · cited 1× · see citing works
“The three-chamber test is a widely-used behavioral test to assess sociability and social recognition [56].”
MethodDe Novo Gene Disruptions in Children on the Autistic Spectrum
Iossifov, I., Ronemus, M., Levy, D., Wang, Z., Hakker, I., Rosenbaum, J., Yamrom, B., Lee, Y.-H., Narzisi, G., Leotta, A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.04.009 · Cited by 1,446 · see citing works
Fmr1 knockout mice: A model to study fragile X mental retardation
THEDUTCHBELGIANFRAGILEXCONSOR (1994) · Cell · doi:10.1016/0092-8674(94)90569-x · Cited by 1,075 · see citing works
Peñagarikano, O., Abrahams, B. S., Herman, E. I., Winden, K. D., Gdalyahu, A., Dong, H., Sonnenblick, L. I., Gruver, R., Almajano, J., Bragin, A., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.040 · Cited by 1,075 · see citing works
Self-citationMaternal influenza infection causes marked behavioral and pharmacological changes in the offspring
Shi, L., Fatemi, S. H., Sidwell, R. W., & Patterson, P. H. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00297.2003 · Cited by 1,025 · see citing works
Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype?
Gerlai, R. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)20020-7 · Cited by 881 · see citing works
Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains
MOY, S., NADLER, J., YOUNG, N., PEREZ, A., HOLLOWAY, L., BARBARO, R., BARBARO, J., WILSON, L., THREADGILL, D., & LAUDER, J. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.07.030 · Cited by 776 · see citing works
Impairment in movement skills of children with autistic spectrum disorders
Green, D., Charman, T., Pickles, A. R., Chandler, S., Loucas, T., Simonoff, E. A., & Baird, G. (2009) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2008.03242.x · Cited by 742 · see citing works
Recurrent 16p11.2 microdeletions in autism
Kumar, R. A., KaraMohamed, S., Sudi, J., Conrad, D. F., Brune, C., Badner, J. A., Gilliam, T. C., Nowak, N. J., Cook, E. H., Dobyns, W. B., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm376 · Cited by 731 · see citing works
Association Between Microdeletion and Microduplication at 16p11.2 and Autism
Weiss, L. A., Shen, Y., Korn, J. M., Arking, D. E., Miller, D. T., Fossdal, R., Sæmundsen, E., Stefánsson, H., Ferreira, M. A. R., Green, T. J., et al. (2008) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000316305.61461.6f · Cited by 647 · see citing works
Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2
Strauss, K. A., Puffenberger, E. G., Huentelman, M. J., Gottlieb, S., Dobrin, S. E., Parod, J. M., Stephan, D. A., & Morton, D. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052773 · Cited by 630 · see citing works
Prenatal Poly(I:C) Exposure and Other Developmental Immune Activation Models in Rodent Systems
Meyer, U. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.011 · Cited by 626 · see citing works
Ultrasonic vocalizations as indices of affective states in rats
Knutson, B., Burgdorf, J., & Panksepp, J. (2002) · Psychological Bulletin · doi:10.1037/0033-2909.128.6.961 · Cited by 618 · see citing works
Automated Three‐Chambered Social Approach Task for Mice
Yang, M., Silverman, J. L., & Crawley, J. N. (2011) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0826s56 · Cited by 598 · see citing works
Shinawi, M., Liu, P., Kang, S.-H. L., Shen, J., Belmont, J. W., Scott, D. A., Probst, F. J., Craigen, W. J., Graham, B. H., Pursley, A., et al. (2010) · Journal of Medical Genetics · doi:10.1136/jmg.2009.073015 · Cited by 580 · see citing works
(1994) · PubMed · Cited by 565 · see citing works
Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1
Poliak, S., Salomon, D., Elhanany, H., Sabanay, H., Kiernan, B. W., Pevny, L., Stewart, C., Xu, X.-R., Chiu, S., Shrager, P., et al. (2003) · Journal of Cell Biology · doi:10.1083/jcb.200305018 · Cited by 542 · see citing works
Self-citationBrain anatomy and sensorimotor gating in Asperger's syndrome
McAlonan, G. M. (2002) · Brain · doi:10.1093/brain/awf150 · Cited by 447 · see citing works
Ingram, J. L., Peckham, S. M., Tisdale, B., & Rodier, P. M. (2000) · Neurotoxicology and Teratology · doi:10.1016/s0892-0362(99)00083-5 · Cited by 381 · see citing works
Exogenous and evoked oxytocin restores social behavior in the <i>Cntnap2</i> mouse model of autism
Peñagarikano, O., Lázaro, M. T., Lu, X.-H., Gordon, A., Dong, H., Lam, H. A., Peles, E., Maidment, N. T., Murphy, N. P., Yang, X. W., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.3010257 · Cited by 378 · see citing works
Self-citationZweier, C., de Jong, E. K., Zweier, M., Orrico, A., Ousager, L. B., Collins, A. L., Bijlsma, E. K., Oortveld, M. A. W., Ekici, A. B., Reis, A., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.10.004 · Cited by 345 · see citing works
Central dopamine hyperactivity in rats mimics abnormal acoustic startle response in schizophrenics
Swerdlow, N. R., BRAFF, D. L., Geyer, M. A., & Koob, G. F. (1986) · Biological Psychiatry · doi:10.1016/0006-3223(86)90005-3 · Cited by 341 · see citing works
Dosage-dependent phenotypes in models of 16p11.2 lesions found in autism
Horev, G., Ellegood, J., Lerch, J. P., Son, Y.-E. E., Muthuswamy, L., Vogel, H., Krieger, A. M., Buja, A., Henkelman, R. M., Wigler, M., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1114042108 · Cited by 330 · see citing works
Self-citationA 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders
Zufferey, F., Sherr, E. H., Beckmann, N. D., Hanson, E., Maillard, A. M., Hippolyte, L., Macé, A., Ferrari, C., Kutalik, Z., Andrieux, J., et al. (2012) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2012-101203 · Cited by 326 · see citing works
Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models
Menalled, L., El‐Khodor, B. F., Patry, M., Suárez‐Fariñas, M., Orenstein, S. J., Zahasky, B., Leahy, C. L., Wheeler, V. C., Yang, X. W., MacDonald, M. E., et al. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.05.007 · Cited by 325 · see citing works
Self-citationSchneider, T., Turczak, J., & Przewłocki, R. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300767 · Cited by 298 · see citing works
Betancur, C., Sakurai, T., & Buxbaum, J. D. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.04.003 · Cited by 298 · see citing works
Broekkamp, C. L., Rijk, H. W., Joly-Gelouin, D., & Lloyd, K. L. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90051-8 · Cited by 286 · see citing works
Bijlsma, E. K., Gijsbers, A. C. J., Schuurs-Hoeijmakers, J. H. M., van Haeringen, A., Fransen van de Putte, D. E., Anderlid, B.-M., Lundin, J., Lapunzina, P., Pérez Jurado, L. A., Delle Chiaie, B., et al. (2009) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2009.03.006 · Cited by 282 · see citing works
Sensorimotor gating abnormalities in young males with fragile X syndrome and Fmr1-knockout mice.
Frankland, P. W., Wang, Y., Rosner, B., Shimizu, T., Balleine, B. W., Dykens, E. M., Ornitz, E. M., & Silva, A. J. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001432 · Cited by 275 · see citing works
Phenotypic variability and genetic susceptibility to genomic disorders
Girirajan, S., & Eichler, E. E. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq366 · Cited by 271 · see citing works
Assessing autism-like behavior in mice: Variations in social interactions among inbred strains
BOLIVAR, V, WALTERS, S., & PHOENIX, J. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.09.007 · Cited by 264 · see citing works
Deogracias, R., Yazdani, M., Dekkers, M. P. J., Guy, J., Ionescu, M. C. S., Vogt, K. E., & Barde, Y. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206093109 · Cited by 255 · see citing works
Cage enrichment and mouse behaviour
Wolfer, D. P., Litvin, O. I., Morf, S., Nitsch, R. M., Lipp, H., & Würbel, H. (2004) · Nature · doi:10.1038/432821a · Cited by 245 · see citing works
Portmann, T., Yang, M., Mao, R., Panagiotakos, G., Ellegood, J., Dolen, G., Bader, P. L., Grueter, B. A., Goold, C., Fisher, E., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.036 · Cited by 245 · see citing works
DeCoteau, W. E., Thorn, C. A., Gibson, D. J., Courtemanche, R., Mitra, P. P., Kubota, Y., & Graybiel, A. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700818104 · Cited by 239 · see citing works
Gemelli, T., Berton, O., Nelson, E. D., Perrotti, L. I., Jaenisch, R., & Monteggia, L. M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.07.025 · Cited by 237 · see citing works
Bachmann‐Gagescu, R., Mefford, H. C., Cowan, C. A., Glew, G. M., Hing, A. V., Wallace, S. E., Bader, P. I., Hamati, A. I., Reitnauer, P. J., Smith, R., et al. (2010) · Genetics in Medicine · doi:10.1097/gim.0b013e3181ef4286 · Cited by 231 · see citing works
Female mice respond to male ultrasonic ‘songs’ with approach behaviour
Hammerschmidt, K., Radyushkin, K., Ehrenreich, H., & Fischer, J. (2009) · Biology Letters · doi:10.1098/rsbl.2009.0317 · Cited by 226 · see citing works
Chemistry of male dominance in the house mouse,Mus domesticus
Novotný, M. V., Harvey, S. C., & Jemioło, B. (1990) · Cellular and Molecular Life Sciences · doi:10.1007/bf01955433 · Cited by 218 · see citing works
Disruption of functional organization within the primary motor cortex in children with autism
Nebel, M. B., Joel, S. E., Muschelli, J., Barber, A. D., Caffo, B. S., Pekar, J. J., & Mostofsky, S. H. (2014) · Human Brain Mapping · doi:10.1002/hbm.22188 · Cited by 213 · see citing works
Motor impairment in sibling pairs concordant and discordant for autism spectrum disorders
Hilton, C. L., Zhang, Y., Whilte, M. R., Klohr, C. L., & Constantino, J. N. (2011) · Autism · doi:10.1177/1362361311423018 · Cited by 211 · see citing works
Disorganized rhythm and synchrony: Early signs of autism and Rett syndrome
Trevarthen, C., & Daniel, S. W. (2005) · Brain and Development · doi:10.1016/j.braindev.2005.03.016 · Cited by 201 · see citing works
Egashira, N., Tanoue, A., Matsuda, T., Koushi, E., Harada, S., Takano, Y., Tsujimoto, G., 三島, 健., Iwasaki, K., & Fujiwara, M. (2006) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.12.009 · Cited by 193 · see citing works
Kondo, M., Gray, L. J., Pelka, G. J., Christodoulou, J., Tam, P. P. L., & Hannan, A. J. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06305.x · Cited by 190 · see citing works
Evidence for Specificity of Motor Impairments in Catching and Balance in Children with Autism
Ament, K. A., Mejia, A. F., Buhlman, R., Erklin, S., Caffo, B. S., Mostofsky, S. H., & Wodka, E. L. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-014-2229-0 · Cited by 186 · see citing works
Ultrasonic vocalizations by rat pups in the cold: An acoustic by-product of laryngeal braking?
BLUMBERG, M. S., & Alberts, J. R. (1990) · Behavioral Neuroscience · doi:10.1037//0735-7044.104.5.808 · Cited by 185 · see citing works
Njung'e, K., & Handley, S. L. (1991) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1991.tb12392.x · Cited by 183 · see citing works
FMR1 Knockout mice: A model to study fragile X mental retardation
Oostra, B. A., Bakker, C. E., & Reyniers, E. (1994) · The American Journal of Human Genetics · Cited by 181 · see citing works
Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice
Pietropaolo, S., Guilleminot, A., Martin, B., D'Amato, F. R., & Crusio, W. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017073 · Cited by 178 · see citing works
Reduced scent marking and ultrasonic vocalizations in the BTBR T+tf/J mouse model of autism
Wöhr, M., Roullet, F. I., & Crawley, J. N. (2011) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2010.00582.x · Cited by 169 · see citing works
Anxiety, motor activation, and maternal–infant interactions in 5HT1B knockout mice.
Brunner, D., Buhot, M.-C., Hen, R., & Hofer, M. A. (1999) · Behavioral Neuroscience · doi:10.1037/0735-7044.113.3.587 · Cited by 168 · see citing works
Self-citationAnxiety, motor activation, and maternal-infant interactions in 5HT-sub(1B ) knockout mice.
Brunner, D., Buhot, M.-C., Hen, R., & Hofer, M. A. (1999) · Behavioral Neuroscience · doi:10.1037//0735-7044.113.3.587 · Cited by 164 · see citing works
Self-citationFine motor skill predicts expressive language in infant siblings of children with autism
LeBarton, E. S., & Iverson, J. M. (2013) · Developmental Science · doi:10.1111/desc.12069 · Cited by 160 · see citing works
Ultrasonic vocalizations by rat pups in the cold: An acoustic by-product of laryngeal braking?
Blumberg, M. S., & Alberts, J. R. (1990) · Behavioral Neuroscience · doi:10.1037/0735-7044.104.5.808 · Cited by 144 · see citing works
Behavioral Phenotyping of Transgenic and Knockout Mice: Practical Concerns and Potential Pitfalls
Bailey, K. R., Rustay, N. R., & Crawley, J. N. (2006) · ILAR Journal · doi:10.1093/ilar.47.2.124 · Cited by 135 · see citing works
Spooren, W., Lindemann, L., Ghosh, A., & Santarelli, L. (2012) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2012.09.004 · Cited by 119 · see citing works
Self-citationThe atypical 16p11.2 deletion: A not so atypical microdeletion syndrome?
Barge‐Schaapveld, D. Q. C. M., Maas, S. M., Polstra, A. M., Knegt, L. C., & Hennekam, R. C. M. (2011) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.33991 · Cited by 119 · see citing works
(1995) · doi:10.1097/00008877-199505001-00026 · Cited by 119 · see citing works
Houghten, R. A., Pinilla, C., Giulianotti, M. A., et al. (2007) · Journal of Combinatorial Chemistry · doi:10.1021/cc7001205 · Cited by 116 · see citing works
Contribution of mGluR5 to pathophysiology in a mouse model of human chromosome 16p11.2 microdeletion
Tian, D., Stoppel, L. J., Heynen, A. J., Lindemann, L., Jaeschke, G., Mills, A. A., & Bear, M. F. (2015) · Nature Neuroscience · doi:10.1038/nn.3911 · Cited by 109 · see citing works
Self-citationRoullet, F., Wöhr, M., & Crawley, J. N. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.06.004 · Cited by 97 · see citing works
Yang, M., Mahrt, E. J., Lewis, F., Foley, G., Portmann, T., Dolmetsch, R. E., Portfors, C. V., & Crawley, J. N. (2015) · Autism Research · doi:10.1002/aur.1465 · Cited by 96 · see citing works
THE MATURATION OF THE PITUITARY-ADRENAL AXIS IN THE NEWBORN RAT1
Jailer, J. W. (1950) · Endocrinology · doi:10.1210/endo-46-5-420 · Cited by 95 · see citing works
Procedural learning and cognitive flexibility in a mouse model of restricted, repetitive behaviour
Tanimura, Y., Yang, M. C. K., & Lewis, M. H. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.01.001 · Cited by 90 · see citing works
High-throughput analysis of behavior for drug discovery
Alexandrov, V., Brunner, D., Hanania, T., & Leahy, E. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.11.047 · Cited by 81 · see citing works
Self-citationAnimal models of Huntington's disease for translation to the clinic: Best practices
Menalled, L., & Brunner, D. (2014) · Movement Disorders · doi:10.1002/mds.26006 · Cited by 79 · see citing works
Self-citationWalsh, K. M., & Bracken, M. B. (2011) · Genetics in Medicine · doi:10.1097/gim.0b013e3182076c0c · Cited by 65 · see citing works
Maternal effects in infant and adult phenotypes of 5HT1A and 5HT1B receptor knockout mice
Weller, A., Leguisamo, A. C., Towns, L., Ramboz, S., Bagiella, E., Hofer, M. A., Hen, R., & Brunner, D. (2003) · Developmental Psychobiology · doi:10.1002/dev.10079 · Cited by 60 · see citing works
Self-citationIn need of high-throughput behavioral systems
Brunner, D., Nestler, E. J., & Leahy, E. (2002) · Drug Discovery Today · doi:10.1016/s1359-6446(02)02423-6 · Cited by 60 · see citing works
Self-citationPeippo, M. M., & Ignatius, J. (2011) · Molecular Syndromology · doi:10.1159/000335287 · Cited by 59 · see citing works
Lehmann, M. L., Geddes, C. E., Lee, J. L., & Herkenham, M. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069822 · Cited by 56 · see citing works
Independence of ultrasonic vocalization and thermogenic responses in infant rats.
Hofer, M. A., & Shair, H. N. (1991) · Behavioral Neuroscience · doi:10.1037//0735-7044.105.1.41 · Cited by 40 · see citing works
High-Throughput Automated Phenotyping of Two Genetic Mouse Models of Huntington's Disease
Balcı, F., Shamy, J. L., El‐Khodor, B. F., Filippov, I., Mushlin, R. A., Port, R. G., Connor, D., Paintdakhi, A., Menalled, L., Ramboz, S., et al. (2013) · PLoS Currents · doi:10.1371/currents.hd.124aa0d16753f88215776fba102ceb29 · Cited by 40 · see citing works
Self-citationCarden, S. E., & Hofer, M. A. (1992) · Behavioral Neuroscience · doi:10.1037//0735-7044.106.2.421 · Cited by 38 · see citing works
Carden, S. E., & Hofer, M. A. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.2.421 · Cited by 35 · see citing works
Roberds, S. L., Filippov, I., Alexandrov, V., et al. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00103 · Cited by 33 · see citing works
Self-citationIndependence of ultrasonic vocalization and thermogenic responses in infant rats.
Hofer, M. A., & Shair, H. N. (1991) · Behavioral Neuroscience · doi:10.1037/0735-7044.105.1.41 · Cited by 33 · see citing works
El‐Khodor, B. F., Dimmler, M. H., Amara, D. A., Hofer, M. A., Hen, R., & Brunner, D. (2004) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2004.06.001 · Cited by 17 · see citing works
Self-citationReprint of: Highthroughtput analysis of behavior for drug discovery
Alexandrov, V., Brunner, D., Hanania, T., et al. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.02.037 · Cited by 8 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [73]Peñagarikano O, Abrahams BS, Herman EI, Winden KD, Gdalyahu A, Dong H, et al Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell. 2011; 147(1): 235– 46. Epub 2011/10/04. S0092-8674(11)01010-5 [pii] 10.1016/j.cell.2011.08.040 21962519 PMC3390029 · DOI · Paper page
Cited by
Sorted by citations
Spratt, P. W. E., Ben-Shalom, R., Keeshen, C. M., Burke, K. J., Clarkson, R. L., Sanders, S. J., & Bender, K. J. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.037 · Cited by 244 · see citing works
Germline Chd8 haploinsufficiency alters brain development in mouse
Gompers, A. L., Su-Feher, L., Ellegood, J., Copping, N. A., Riyadh, M. A., Stradleigh, T. W., Pride, M. C., Schaffler, M. D., Wade, A. A., Catta-Preta, R., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4592 · Cited by 266 · see citing works
Sinclair, D., Oranje, B., Razak, K. A., Siegel, S. J., & Schmid, S. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.029 · Cited by 198 · see citing works
Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat
Harony-Nicolas, H., Kay, M., Hoffmann, J. D., Klein, M. E., Bozdagi-Gunal, O., Riad, M., Daskalakis, N. P., Sonar, S., Castillo, P. E., Hof, P. R., et al. (2017) · eLife · doi:10.7554/elife.18904 · Cited by 168 · see citing works
16p11.2 Copy Number Variations and Neurodevelopmental Disorders
Rein, B., & Yan, Z. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.09.001 · Cited by 160 · see citing works
Measuring behavior in the home cage: study design, applications, challenges, and perspectives
Grieco, F., Bernstein, B. J., Biemans, B., Bikovski, L., Burnett, C. J., Cushman, J. D., van Dam, E. A., Fry, S. A., Richmond-Hacham, B., Homberg, J. R., et al. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.735387 · Cited by 109 · see citing works
Self-citationStoppel, L. J., Kazdoba, T. M., Schaffler, M. D., Preza, A. R., Heynen, A., Crawley, J. N., & Bear, M. F. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.236 · Cited by 92 · see citing works
Hyperactivity and male‐specific sleep deficits in the 16p11.2 deletion mouse model of autism
Angelakos, C. C., Watson, A. J., O'Brien, W. T., Krainock, K. S., Nickl‐Jockschat, T., & Abel, T. (2017) · Autism Research · doi:10.1002/aur.1707 · Cited by 83 · see citing works
Rein, B., Tan, T., Yang, F., Wang, W., Williams, J., Zhang, F., Mills, A., & Yan, Z. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0693-9 · Cited by 58 · see citing works
Self-citationDeep phenotyping reveals movement phenotypes in mouse neurodevelopmental models
Klibaite, U., Kislin, M., Verpeut, J. L., Bergeler, S., Sun, X., Shaevitz, J. W., & Wang, S. S.-H. (2022) · Molecular Autism · doi:10.1186/s13229-022-00492-8 · Cited by 41 · see citing works
Agarwalla, S., Arroyo, N. S., Long, N. E., O'Brien, W. T., Abel, T., & Bandyopadhyay, S. (2020) · Genes, Brain and Behavior · doi:10.1111/gbb.12681 · Cited by 26 · see citing works
- Authors
- Brunner, D., Kabitzke, P., He, D., Cox, K., Thiede, L., Hanania, T., Sabath, E., Alexandrov, V., Saxe, M., Peles, E., Mills, A., Spooren, W., Ghosh, A., Feliciano, P., Benedetti, M., Luo Clayton, A., & Biemans, B.
- Affiliations
- Psychogenics (United States) (US)
- F. Hoffmann-La Roche AG (CH)
- Weizmann Institute of Science (IL)
- Cold Spring Harbor Laboratory (US)
- Simons Foundation (US)
- Corresponding author
- Brunner, Daniela
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-08-14
- Volume
- 10
- Issue
- 8
- Pages
- e0134572
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4537259
- OpenAlex
- W1945406363
- Cited by
- 111
- References
- 89
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 15 · 2023: 9 · 2022: 11 · 2021: 6 · 2020: 22 · 2019: 10 · 2018: 8 · 2017: 11 · 2016: 2
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Columbia Academic Commons (Columbia University)
- Funders
- Simons Foundation
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- autism spectrum disorder, 16p11.2 deletion, CNTNAP2, mouse models of autism, behavioral phenotyping, hyperactivity, social behavior, vocalizations, procedural learning, construct validity
- MeSH terms
- Autism Spectrum Disorder, Animals, Animals, Newborn, Behavior, Animal, Cognition, Disease Models, Animal, Female, Humans, Male, Membrane Proteins, Mutation, Nerve Tissue Proteins, Vocalization, Animal, Sequence Deletion, Chromosomes, Mammalian, 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
