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A Conditional Knockout Mouse Line of the Oxytocin Receptor
Open accessAbstract
Oxytocin plays important roles in reproductive physiology and various behaviors, including maternal behavior and social memory. Its receptor (Oxtr) is present in peripheral tissues and brain, so a conditional knockout (KO, −/−) would be useful to allow elimination of the receptor in specific sites at defined times. We created a line of mice in which loxP sites flank Oxtr coding sequence (floxed) enable Cre recombinase-mediated inactivation of the receptor. We expressed Cre recombinase in these mice either in all tissues (Oxtr−/−) or the forebrain (OxtrFB/FB) using the Ca2+/calmodulin-dependent protein kinase IIα promoter. The latter KO has reduced Oxtr binding beginning 21–28 d postnatally, leading to prominent reductions in the lateral septum, hippocampus, and ventral pallidum. The medial amygdala is spared, and there is significant retention of binding within the olfactory bulb and nucleus and neocortex. We did not observe any deficits in the general health, sensorimotor functions, anxiety-like behaviors, or sucrose intake in either Oxtr−/− or OxtrFB/FB mice. Females of both KO types deliver pups, but only the OxtrFB/FB mice are able to eject milk. Oxtr−/− males show impaired social memory for familiar females, whereas the OxtrFB/FB males appear to recognize their species but not individuals. Our results confirm the importance of oxytocin in social recognition and demonstrate that spatial and temporal inactivation of the Oxtr will enable finer understanding of the physiological, behavioral, and developmental roles of the receptor.
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In the citing paper
“A single intracerebroventricular infusion of OT before, but not after, the initial exposure completely rescues the deficit in social recognition [82].”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [82]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Analysis of neural activation patterns using Fos immunohistochemistry revealed that following a social encounter, Fos activation is normal in the olfactory bulb, but is markedly impaired in the medial amydala and downstream projection sites of the amygdala [82].”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [82]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Site-specific infusion of OT into the medial amygdala, but not into the olfactory bulb rescued the social recognition deficits [82].”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [82]
Experimental — accuracy not yet measuredIn the citing paper
“Similarly, OTR knock-out mice also display significant deficits in social recognition [69; 70; 71; 72].”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [72]
In the citing paper
“The brain areas in which we found alterations of OXT receptors are involved in the regulation of social recognition.”
From Chronic and acute intranasal oxytocin produce divergent social effects in mice (2014) · cites this paper as Lee et al, 2008
In the citing paper
“However, male forebrain Oxtr knockout (Oxtr Fb/Fb) mice (101, 102), in which the Oxtr gene is excised 21–28 days after birth, have normal aggressive behavior in adulthood (100).”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [101]
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Metadata
- Authors
- Lee, H.-J., Caldwell, H. K., Macbeth, A. H., Tolu, S. G., & Young, W. S.
- Affiliations
- National Institutes of Health (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-03-20
- Volume
- 149
- Issue
- 7
- Pages
- 3256-3263
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2453083
- OpenAlex
- W2026117260
- Cited by
- 269
- References
- 43
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 18 · 2023: 9 · 2022: 5 · 2021: 13 · 2020: 33 · 2019: 15 · 2018: 18 · 2017: 25 · 2016: 15 · 2015: 27 · 2014: 13 · 2013: 14 · 2012: 14
- FWCI
- 16.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (Z01MH002498)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Keywords
- oxytocin receptor, conditional knockout mice, Cre recombinase, lateral septum, hippocampus, ventral pallidum, medial amygdala, olfactory bulb, social recognition, social memory, maternal behavior, milk ejection, anxiety-like behavior, sucrose intake
- MeSH terms
- Animals, Autoradiography, Behavior, Animal, Eating, Female, Genotype, Male, Memory, Mice, Inbred Strains, Phenotype, Sucrose, Time Factors, Blotting, Southern, Prosencephalon, Receptors, Oxytocin, Mice, Knockout, Integrases, Recognition, Psychology, Mice
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