Ultrasonic vocalizations in Shank mouse models for autism spectrum disorders: Detailed spectrographic analyses and developmental profiles
Abstract
Autism spectrum disorders (ASD) are a class of neurodevelopmental disorders characterized by persistent deficits in social behavior and communication across multiple contexts, together with repetitive patterns of behavior, interests, or activities. The high concordance rate between monozygotic twins supports a strong genetic component. Among the most promising candidate genes for ASD is the SHANK gene family, including SHANK1, SHANK2 (ProSAP1), and SHANK3 (ProSAP2). SHANK genes are therefore important candidates for modeling ASD in mice and various genetic models were generated within the last few years. As the diagnostic criteria for ASD are purely behaviorally defined, the validity of mouse models for ASD strongly depends on their behavioral phenotype. Behavioral phenotyping is therefore a key component of the current translational approach and requires sensitive behavioral test paradigms with high relevance to each diagnostic symptom category. While behavioral phenotyping assays for social deficits and repetitive patterns of behavior, interests, or activities are well-established, the development of sensitive behavioral test paradigms to assess communication deficits in mice is a daunting challenge. Measuring ultrasonic vocalizations (USV) appears to be a promising strategy. In the first part of the review, an overview on the different types of mouse USV and their communicative functions will be provided. The second part is devoted to studies on the emission of USV in Shank mouse models for ASD. Evidence for communication deficits was obtained in Shank1, Shank2, and Shank3 genetic mouse models for ASD, often paralleled by behavioral phenotypes relevant to social deficits seen in ASD.
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Shank2−/− and Shank3−/− mutant mice show reduction in the number and duration of ultrasonic vocalizations associated with diminished sociability.
“female–female social interactions and USV have been analyzed in Shank2−/− and Shank3−/− mutant mice showing reduction in the number and duration of USVs associated with diminished sociability (Schmeisser, et al. 2012; Ey, et al. 2013; Wohr 2014).”
From <i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as Wohr 2014
Shank1-/- and Shank3B-/- mice display behavioral phenotypes with relevance to all core symptoms of ASD in humans.
“The two models display behavioral phenotypes with relevance to all core symptoms of ASD in humans [38–40]”
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Gong, X., Jiang, Y.-W., Zhang, X., An, Y., Zhang, J., Wu, Y., Wang, J., Sun, Y., Liu, Y., Gao, X., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034739 · Cited by 46 · see citing works
Wöhr, M., Moles, A., Schwarting, R. K. W., & D'Amato, F. R. (2010) · Social Neuroscience · doi:10.1080/17470911003765560 · Cited by 45 · see citing works
Self-citationThe autism diagnosis in translation: shared affect in children and mouse models of ASD
Bishop, S. L., & Lahvis, G. P. (2011) · Autism Research · doi:10.1002/aur.216 · Cited by 40 · see citing works
Rowlett, J. K., Tornatzky, W., Cook, J. M., et al. (2001) · PubMed · Cited by 33 · see citing works
Modeling Social Communication Deficits in Mouse Models of Autism
Michetti, C. (2012) · Autism - Open Access · doi:10.4172/2165-7890.s1-007 · Cited by 29 · see citing works
Rowlett, J. K., Tornatzky, W., Cook, J. M., et al. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29534-3 · Cited by 20 · see citing works
Ultrasonic calls produced by three laboratory strains of Mus musculus
Robinson, D. J., & D’Udine, B. (1982) · Journal of Zoology · doi:10.1111/jzo.1982.197.3.383 · Cited by 19 · see citing works
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Filice, F., Vörckel, K. J., Sungur, A. Ö., Wöhr, M., & Schwaller, B. (2016) · Molecular Brain · doi:10.1186/s13041-016-0192-8 · Cited by 240 · see citing works
Self-citationMeasuring 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
Deliu, E., Arecco, N., Morandell, J., Dotter, C. P., Contreras, X., Girardot, C., Käsper, E.-L., Kozlova, A., Kishi, K., Chiaradia, I., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0266-2 · Cited by 89 · see citing works
Rigney, N., Whylings, J., Mieda, M., de Vries, G. J., & Petrulis, A. (2019) · eNeuro · doi:10.1523/eneuro.0415-18.2019 · Cited by 63 · see citing works
“, 2008b), all aspects of mouse communication known to show pronounced sex differences (Crawley, 2012; Lehmann et al., 2013; Wöhr, 2014).”
BackgroundGranon, S., Faure, A., Chauveau, F., Cressant, A., & Ey, E. (2018) · Handbook of Behavioral Neuroscience · doi:10.1016/b978-0-12-809600-0.00040-8 · Cited by 33 · see citing works
<i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution
Levi, G., de Lombares, C., Giuliani, C., Iannuzzi, V., Aouci, R., Garagnani, P., Franceschi, C., Grimaud-Hervé, D., & Narboux-Nême, N. (2021) · Molecular Biology and Evolution · doi:10.1093/molbev/msab181 · Cited by 29 · see citing works
“Other “language-associated” genes include for example SHANK1/2/3, FOXP1, GNPTAB, GNPTG, CNTNAP2, and NAGPA; for most of these genes mouse models have been generated resulting almost invariably in alteration of USV and social behavior (Wohr 2014; Caruso, et al. 2020).”
BackgroundMethodInfluentialRigney, N., Zbib, A., de Vries, G. J., & Petrulis, A. (2022) · Journal of Neuroendocrinology · doi:10.1111/jne.13083 · Cited by 29 · see citing works
- Authors
- Wöhr, M.
- Affiliations
- Philipps University of Marburg (DE)
- Corresponding author
- Wöhr, Markus
- ORCID
- Wöhr, Markus
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 43
- Pages
- 199-212
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W1992667293
- Cited by
- 107
- References
- 103
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 6 · 2023: 8 · 2022: 9 · 2021: 14 · 2020: 12 · 2019: 10 · 2018: 9 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 3
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute for Health and Care Research
- National Institutes of Health
- 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 › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Animal Vocal Communication and Behavior
- Keywords
- autism spectrum disorder, ultrasonic vocalizations, Shank1, Shank2, SHANK3, communication difficulties, social dysfunction, behavioral phenotyping, mouse models of autism, developmental profile, spectrographic analysis
- MeSH terms
- Animals, Developmental Disabilities, Child Development Disorders, Pervasive, Disease Models, Animal, Humans, Phenotype, Social Behavior, Vocalization, Animal, Mice
About these checks
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