CRISPR-Cas9 editing of the arginine-vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters
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Studies from a variety of species indicate that arginine–vasopressin (AVP) and its V1a receptor (Avpr1a) play a critical role in the regulation of a range of social behaviors by their actions in the social behavior neural network. To further investigate the role of AVPRs in social behavior, we performed CRISPR-Cas9–mediated editing at the Avpr1a gene via pronuclear microinjections in Syrian hamsters (Mesocricetus auratus), a species used extensively in behavioral neuroendocrinology because they produce a rich suite of social behaviors. Using this germ-line gene-editing approach, we generated a stable line of hamsters with a frame-shift mutation in the Avpr1a gene resulting in the null expression of functional Avpr1as. Avpr1a knockout (KO) hamsters exhibited a complete lack of Avpr1a-specific autoradiographic binding throughout the brain, behavioral insensitivity to centrally administered AVP, and no pressor response to a peripherally injected Avpr1a-specific agonist, thus confirming the absence of functional Avpr1as in the brain and periphery. Contradictory to expectations, Avpr1a KO hamsters exhibited substantially higher levels of conspecific social communication (i.e., odor-stimulated flank marking) than their wild-type (WT) littermates. Furthermore, sex differences in aggression were absent, as both male and female KOs exhibited more aggression toward same-sex conspecifics than did their WT littermates. Taken together, these data emphasize the importance of comparative studies employing gene-editing approaches and suggest the startling possibility that Avpr1a-specific modulation of the social behavior neural network may be more inhibitory than permissive.
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Constitutive knockout of Avpr1a in Syrian hamsters paradoxically increased flank marking and aggression in both sexes, highlighting the complex role of Avpr1a in territorial behaviors and potentially highlighting the role of compensatory mechanisms and/or effects on Avpr1a knockout in multiple brain regions.
“Recently, constitutive KO of Avpr1a in Syrian hamsters paradoxically increased flank marking and aggression in both sexes, highlighting the complex role of Avpr1a in territorial behaviors and potentially highlighting the role of compensatory mechanisms and/or effects on Avpr1a KO in multiple brain regions (118).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [118]
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- [49]National Research Council, Guide for the Care and Use of Laboratory Animals (National Academies Press, Washington, DC, ed. 8, 2011).
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Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities
Rigney, N., de Vries, G. J., Petrulis, A., & Young, L. J. (2022) · Endocrinology · doi:10.1210/endocr/bqac111 · Cited by 191 · see citing works
- Authors
- Taylor, J. H., Walton, J. C., McCann, K. E., Norvelle, A., Liu, Q., Vander Velden, J. W., Borland, J. M., Hart, M., Jin, C., Huhman, K. L., Cox, D. N., & Albers, H. E.
- Affiliations
- Georgia State University (US)
- Neuroscience Institute, Georgia State University, Atlanta, GA 30303
- Corresponding author
- Albers, H. Elliott
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2022-05-05
- Volume
- 119
- Issue
- 19
- Pages
- e2121037119-e2121037119
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC9171636
- OpenAlex
- W4229052858
- Cited by
- 35
- References
- 53
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 9 · 2023: 12 · 2022: 5
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (IOS-1035960)
- National Institute of Mental Health (MH109302, MH122622)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- vasopressin, V1a receptor, AVPR1A, CRISPR/Cas9 genome editing, golden hamster, social behavior, flank marking, aggression, sex differences in aggression, frameshift mutation, knockout mice
- MeSH terms
- Aggression, Animals, Arginine, Arginine Vasopressin, Cricetinae, Mesocricetus, Social Behavior, Receptors, Vasopressin, CRISPR-Cas Systems
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