Behavioural studies using temporal and spatial inactivation of the oxytocin receptor
Abstract
Oxytocin (Oxt), synthesized in magnocellular neurons of the paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei for transport to and release from the posterior pituitary, is released during parturition and is essential for lactation. Lesser amounts of Oxt are made by smaller cells of the PVN and a few other forebrain nuclei and released into the central nervous system (CNS) to influence various other behaviours. In both the periphery and CNS, Oxt actions are transduced by the oxytocin receptor (Oxtr). Previously, it has been reported that Oxt(-/-) (knockout, KO) mice show a failure of milk ejection and thus are incapable of rearing their offspring. Unexpectedly, these mice have largely normal reproductive and maternal behaviours, perhaps due to compensatory mechanisms through activation of the Oxtr by vasopressin or through development. To examine the specific roles of the Oxtr during development and in particular brain areas, we created conditional Oxtr(-/-) mice in which we could control the spatial and temporal inactivation of the Oxtr. We flanked the neomycin-resistance selectable marker in an Oxtr intron with FRT sites to enable its removal using FLP recombinase. Coding sequence within exons 2 and 3 was flanked by two loxP sites enabling subsequent inactivation of the gene by targeted expression of Cre recombinase. The first Oxtr KO lines we created have either total or relatively specific forebrain elimination. The latter was achieved by crossing the conditional Oxtr line with a transgenic line in which the Camk2a promoter drives expression of Cre recombinase to significant levels beginning 21-28 days after birth, thus eliminating potential compensation for a deleted Oxtr gene during early development. This Cre-expressing line also significantly spares the main olfactory bulb reducing the potential confound of an olfactory deficit. We have investigated various behaviours, most notably social recognition, in both Oxtr KO strains (Oxtr(-/-) and Oxtr(FB/FB)).
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Male forebrain Oxtr knockout mice, in which the Oxtr gene is excised 21-28 days after birth, have normal aggressive behavior in adulthood.
“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 [102]
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- Authors
- LEE, H., CALDWELL, H., MACBETH, A., & YOUNGIII, W.
- Affiliations
- United States Department of Health and Human Services (US)
- Kent State University (US)
- ORCID
- Venue
- Progress in brain research
- Publisher
- Elsevier
- Published
- 2008
- Volume
- 170
- Pages
- 73-77
- ISSN
- 0079-6123 (ISSN-L)
- OpenAlex
- W1559167201
- Cited by
- 49
- References
- 27
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 2 · 2013: 5 · 2012: 7
- FWCI
- 5.01
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Progress in brain research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Social Sciences › Psychology › Social Psychology › 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, oxytocin, conditional knockout mice, Cre-loxP system, social recognition, maternal behavior, reproductive behavior, vasopressin, paraventricular nucleus, supraoptic nucleus, neomycin resistance
- MeSH terms
- Animals, Behavior, Animal, Gene Expression Regulation, Phenotype, Space Perception, Time Perception, Receptors, Oxytocin, Mice, Knockout, Recognition, Psychology, Mice
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