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Mapping oxytocin receptor gene expression in the mouse brain and mammary gland using an oxytocin receptor-LacZ reporter mouse
Abstract
The hypothalamic nonapeptide oxytocin (OT) has an established role as a circulating hormone but can also act as a neurotransmitter and as a neuromodulator by interacting with its central OT receptor (OTR). To understand the role of the OTR in the mouse brain we investigated the expression of the OTR gene at the cellular level. We targeted the lacZ reporter gene to the OTR gene locus downstream of the endogenous OTR regulatory elements. Using lactating mouse mammary gland as a control for OTR promoter directed specificity of lacZ gene expression, X-gal histochemistry on tissue sections confirmed that gene expression was restricted to the myoepithelial cells. We also identified for the first time in mice the expression of the OTR gene in neighbouring adipocytes. Further, investigation in the mouse brain identified numerous nuclei containing neurons expressing the OTR gene. Whilst some of these regions had been described for rat or sheep, the OTR-LacZ reporter mouse enabled the identification of novel sites of central OTR gene expression. These regions include the accessory olfactory bulb, the medial septal nucleus, the posterolateral cortical amygdala nucleus, the posterior aspect of the basomedial amygdala nucleus, the medial part of the supramammillary nucleus, the dorsotuberomammillary nucleus, the medial and lateral entorhinal cortices, as well as specific dorsal tegmental, vestibular, spinal trigeminal, and solitary tract subnuclei. By mapping the distribution of OTR gene…
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“It has been previously shown that adipocytes and fat progenitor cells have receptors for oxytocin(35, 36).”
From Oxytocin reduces caloric intake in men (2015) · cites this paper as [35]
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Maejima, Y., Horita, S., Yokota, S., Ono, T., Proks, P., Yoshida‐Komiya, H., Ueta, Y., Nishimori, K., Misaka, S., & Shimomura, K. (2021) · Journal of Food and Drug Analysis · doi:10.38212/2224-6614.3381 · Cited by 13
Lindenmaier, Z., Ellegood, J., Stuive, M., Easson, K., Yee, Y., Fernandes, D., Foster, J., Anagnostou, E., & Lerch, J. (2021) · bioRxiv · doi:10.1101/2021.01.13.426562 · Cited by 10
Dhungel, S., Rai, D., Terada, M., Orikasa, C., Nishimori, K., Sakuma, Y., & Kondo, Y. (2018) · Neuroscience Research · doi:10.1016/j.neures.2018.11.008 · Cited by 15
The MAP kinase ERK5/MAPK7 is a downstream effector of oxytocin signaling in myometrial cells.
Devost, D., Zingg, H., & Hébert, T. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110211 · Cited by 8
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“The symbol # indicates differences between treatments at p < 0.05.”
BackgroundInfluentialImam, B., Rahmatinia, M., Shahsavani, A., Khodagholi, F., Hopke, P. K., Bazzazpour, S., Hadei, M., Yarahmadi, M., Abdollahifar, M., Torkmahalleh, M. A., et al. (2022) · Environmental Science and Pollution Research · doi:10.1007/s11356-022-19865-w · Cited by 5
“The OXT receptor (OXTRs) are abundant in brain regions such as the olfactory lobe, hippocampus, hypothalamus, and amygdala (Gould and Zingg 2003), where they collaborate for regulation of the social, emotional,”
RetractedThe Role of Oxytocin in Neuropsychiatric Disorders: Concepts and Mechanisms
Levin, R., Edelman, S., Shalev, I., Ebstein, R. P., & Heresco‐Levy, U. (2010) · Springer eBooks · doi:10.1007/978-90-481-8553-5_20 · Cited by 5
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“OT operates through its receptor, expressed in the amygdala, hippocampus, NAcc, and hypothalamus (Geerling et al., 2010; Gould and Zingg, 2003; Vaidyanathan and Hammock, 2017).”
Conditional oxytocin receptor knockout mice: targeting the forebrain to understand behavior.
Amico, J. (2008) · Endocrinology · doi:10.1210/en.2008-0463 · Cited by 5
“However, in most species the OTR is abundant in brain regions such as the amygdala, hippocampus, olfactory lobe, and hypothalamus (11, 12), which regulate many of the social, emotional, and neuroendocrine behaviors that OT is hypothesized to influence.”
BackgroundHistological analysis of neuronal changes in the olfactory cortex during pregnancy
Matsuda, K., Takahashi, T., Morishita, S., & Tanaka, M. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e26780 · Cited by 7
“Analysis of expression of receptors for pregnancy-related peptide hormones showed expression of OT-R in both olfactory cortex regions [45] and distribution of OT-positive neurites in these regions.”
BackgroundBehavioral plasticity: Role of neuropeptides in shaping feeding responses
Levine, A. S., Jewett, D. C., Kotz, C. M., & Olszewski, P. K. (2022) · Appetite · doi:10.1016/j.appet.2022.106031 · Cited by 5
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“…ModelBR-1365; No. of Pages 15 2 J. Hahn-Holbrook et al. / Neuroscience a edial amygdala is dedicated to processing socially relevant cues, he highest levels of oxytocin receptor gene expression observed in he mouse amygdala have been found within the medial amygdala Gould and Zingg, 2003).”
Epigenetics and Neuroendocrinology
Binder, E. B., & Spengler, D. (2016) · Epigenetics and human health · doi:10.1007/978-3-319-29901-3 · Cited by 4
Chavez, J., Le, A. A., Lauterborn, J. C., Cox, B. M., Jia, Y., LYNCH, G. S., & Gall, C. M. (2026) · Neuropsychopharmacology · doi:10.1038/s41386-026-02423-0 · Cited by 3
Manella, L. C., Woldeyohannes, L., McMahon, D., & Linster, C. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.12.002 · Cited by 3
Teruyama, R., & Govar, A. A. (2024) · Peptides · doi:10.1016/j.peptides.2024.171283 · Cited by 1
Oxytocin as a Metabolic Modulator
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Air pollutants reinforce autism–like behavior in the VPA-Induced – rat model of autismPreprint
Emam, B., Shahsavani, A., Khodagholi, F., Hopke, P. K., Abdollahifar, M., Hadei, M., & Mirbehbahani, S. H. (2020) · doi:10.21203/rs.3.rs-21729/v1
“OXTRs are abundant in brain areas such as the amygdala, hippocampus, olfactory lobe, and hypothalamus [56], where they are thought to be involved in the regulation of the emotional, social, and neuroendocrine behaviors [58].”
BackgroundDi, T.-Q., Huang, Y., & Gao, J. (2020) · Advances in Psychological Science · doi:10.3724/sp.j.1042.2020.00456 · Cited by 1
“…产后抑郁症严重破坏了女性的认知功能, 导 致患者无法正常地表达母性行为。自我报告显示 患者无法长时间集中注意力, 工作记忆的容量变 低 , 言语表达能力的流畅性变差(Nguyen, 2017), 以上均对母婴互动的质量产生了消极的影响。不 良的认知风格也是抑郁症的核心表现, 已有研究 发现自我牺牲和高标准的信念是患有产后抑郁症 女性的普遍特征(O'Mahen, Flynn, Nolen-Hoeksema, & Psychology, 2010), 伴随着对其母亲角色的过 度批判性评估(Gelabert et al., 2012)。未能达到这…”
Central and peripheral oxytocin profiles during milking in ewes
Bochini, J. C., Alvisi, R., Negrão, J. A., Engelberg-Cook, E., & Felício, L. F. (2014) · Brazilian Journal of Veterinary Research and Animal Science · doi:10.11606/issn.1678-4456.v51i1p68-77 · Cited by 1
Brain and Cardiovascular Diseases: Molecular Aspects
Szczepanska‐Sadowska, E. K. (2013) · doi:10.1002/9781118395318.ch27
Genome editing-based refinement of GPCR visualization in mice using the oxytocin receptor as a model
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“To examine this more comprehensively, we analyzed three cell types known to express Oxtr: neurons in the cerebral cortex 26 , pancreatic islet cells 33 , and mammary myoepithelial cells 34 , using high-magnification imaging of homozygous adult mice.”
Martin, T. J., Martin, C. W., Murulikanth, N., Parker, R., Fonseca, M. M., Romero-Sandoval, E. A., Peters, C. M., Abbott, J., Gordon, S., Zhao, G., et al. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.09.026
Rastoldo, G., Marouane, E., El-Mahmoudi, N., Péricat, D., & Tighilet, B. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315262
“The behavioral effects of oxytocin on UVN rats may be the result of a direct action on the vestibular nuclei (the presence of the oxytocin receptor in vestibular nuclei: [18,19]) or an indirect action on other brain structures.”
BackgroundEffectiveness of Japanese herbal medicines (Kampo) for stress
Tsukada, M., Ikemoto, H., Inoue, T., Kojima, E., Fukuoka, S., & Sunagawa, M. (2021) · Equilibrium Research · doi:10.3757/jser.80.296
Méquinion, M. (2014) · theses.fr (ABES) · doi:10.70675/8164dbbcz3c72z46f4za0d8z22289b73b5e3
Bochini, J. C. (2008) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.10.2008.tde-18112008-153251
Baudon, A., Creusot, E. C., & Charlet, A. (2022) · Biologie Aujourd hui · doi:10.1051/jbio/2022022 · Cited by 1
“…noter ici que, bien que l ’ expression de l ’ OTR dans les neurones soit observée chez une myriade d ’ espèces et dans de nombreuses régions du cerveau (Gould & Zingg, 2003 ; Mitre et al. , 2016 ; Newmaster et al. , 2020 ; Young & Song, 2020), les études réalisées jusqu ’ à présent n ’ ont pas…”
Young, L. J., & Zingg, H. H. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803592-4.00056-0
Oxytocin Receptors and Neurobehavior
Kumsta, R., Zang, J. C. S., & Moser, D. (2016) · Epigenetics and human health · doi:10.1007/978-3-319-29901-3_10
Metadata
- Authors
- Gould, B. R., & Zingg, H. H.
- Affiliations
- Royal Victoria Hospital (CA)
- Corresponding author
- Zingg, H.H
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 122
- Issue
- 1
- Pages
- 155-167
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2035269878
- Cited by
- 138
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 11 · 2021: 11 · 2020: 7 · 2019: 4 · 2018: 10 · 2017: 7 · 2016: 10 · 2015: 8 · 2014: 12 · 2013: 10 · 2012: 4
- FWCI
- 3.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- oxytocin receptor, gene expression mapping, myoepithelial cells, mammary gland, amygdala, accessory olfactory bulb, supramammillary nucleus, entorhinal cortex, oxytocinergic system, adipocytes
- MeSH terms
- Animals, Brain, Female, Lac Operon, Mammary Glands, Animal, Mice, Transgenic, Blotting, Southern, Gene Expression, Receptors, Oxytocin, Reverse Transcriptase Polymerase Chain Reaction, Mice
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