Oxytocin receptor knockout prairie voles generated by CRISPR/Cas9 editing show reduced preference for social novelty and exaggerated repetitive behaviors
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Behavioral neuroendocrinology has benefited tremendously from the use of a wide range of model organisms that are ideally suited for particular questions. However, in recent years the ability to manipulate the genomes of laboratory strains of mice has led to rapid advances in our understanding of the role of specific genes, circuits and neural populations in regulating behavior. While genome manipulation in mice has been a boon for behavioral neuroscience, the intensive focus on the mouse restricts the diversity in behavioral questions that can be investigated using state-of-the-art techniques. The CRISPR/Cas9 system has great potential for efficiently generating mutants in non-traditional animal models and consequently to reinvigorate comparative behavioral neuroendocrinology. Here we describe the efficient generation of oxytocin receptor (Oxtr) mutant prairie voles (Microtus ochrogaster) using the CRISPR/Cas9 system, and describe initial behavioral phenotyping focusing on behaviors relevant to autism. Oxtr mutant male voles show no disruption in pup ultrasonic vocalization, anxiety as measured by the open field test, alloparental behavior, or sociability in the three chamber test. Mutants did however show a modest elevation in repetitive behavior in the marble burying test, and an impairment in preference for social novelty. The ability to efficiently generate targeted mutations in the prairie vole genome will greatly expand the utility of this model organism for discovering the genetic and circuit mechanisms underlying complex social behaviors, and serves as a proof of principle for expanding this approach to other non-traditional model organisms.
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CRISPR-generated oxytocin receptor knockout and oxytocin receptor-Cre prairie voles provide a means for elucidating the function of oxytocin signaling and social bonding.
“CRISPR-generated oxytocin receptor knockout and oxytocin receptor–Cre prairie voles provide a means for elucidating the function of oxytocin signaling and social bonding (Horie et al. 2019, 2020).”
From Oxytocin, Neural Plasticity, and Social Behavior (2021) · cites this paper as Horie et al. 2019
Oxtr knockout prairie voles display altered social preferences and reduced helping behavior toward a familiar cagemate.
“Oxtr KO prairie voles display altered social preferences and reduced helping behavior toward a familiar cagemate (27,147).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [27]
Oxytocin receptor knockout voles demonstrated autism-like behavior such as a lack of interest in social novelty.
“A previous study reported that oxytocin receptor knockout voles demonstrated autism-like behavior such as a lack of interest in social novelty (Horie et al., 2019).”
From Helping behavior in prairie voles: a model of empathy and the importance of oxytocin (2022) · cites this paper as Horie et al., 2019
In a previous study, there was no significant difference in activity level in an open field test between Oxtr KO and wild-type voles.
“However, in a previous study, there was no significant difference in activity level in an open field test between Oxtr KO and wild-type voles (Horie et al., 2019).”
From Helping behavior in prairie voles: a model of empathy and the importance of oxytocin (2022) · cites this paper as Horie et al., 2019
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“OXTR autoradiography was performed as described previously (Horie et al., 2019).”
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Oxytocin Ameliorates Impaired Behaviors of High Fat Diet-Induced Obese Mice
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Mean Girls: Social Stress Models for Female Rodents
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Maturation of Social-Vocal Communication in Prairie Vole (Microtus ochrogaster) Pups
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Oxytocin receptor is a promising therapeutic target of malignant mesothelioma
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- Authors
- Horie, K., Inoue, K., Suzuki, S., Adachi, S., Yada, S., Hirayama, T., Hidema, S., Young, L. J., & Nishimori, K.
- Affiliations
- Tohoku University (JP)
- Emory University (US)
- Juntendo University (JP)
- University of Tsukuba (JP)
- Corresponding author
- Young, Larry J.
- Nishimori, Katsuhiko
- ORCID
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 111
- Pages
- 60-69
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC6506400
- OpenAlex
- W2899697565
- Cited by
- 77
- References
- 74
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 12 · 2022: 11 · 2021: 18 · 2020: 11 · 2019: 5
- FWCI
- 11.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- JSPS (15H02442 (2015–2018), 16K15698 (2016–2017), 16J05070 (2016-2019))
- MEXT (16H01480 (2016-2017))
- Japan Agency for Medical Research and Development (18dm0107076h0003 (2016-2020))
- NIH (R01MH096983, R01MH112788, R21MH114151, P50MH100023, P51OD11132)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- oxytocin receptor, Microtus ochrogaster, CRISPR/Cas9 genome editing, social novelty preference, repetitive behavior, autism model, anxiety, sociability, social behavior genetics
- MeSH terms
- Gene Editing, Animals, Anxiety, Autistic Disorder, Arvicolinae, Exploratory Behavior, Female, Male, Obsessive Behavior, Oxytocin, Social Behavior, Receptors, Oxytocin, Animals, Genetically Modified, Mice, Gene Knockdown Techniques, CRISPR-Cas Systems
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