Structure and expression of the mouse oxytocin receptor gene

Kubota, Yasue; Kimura, Tadashi; Hashimoto, Kazumasa; Tokugawa, Yoshihiro; Nobunaga, Katsutoshi; Azuma, Chihiro; Saji, Fumitaka; Murata, Yuji

doi:10.1016/s0303-7207(96)03923-8

Cited by 87 publications

(51 citation statements)

References 22 publications

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“…The gene for OTR was found to be a single copy, mapped at 3p25-3p26·2 in the human genome (Inoue et al 1994). Presently, the gene structures from several species, including the rat (Rozen et al 1995), bovine (Bathgate et al 1995), mouse (Kubota et al 1996) and vole (Young et al 1996) are available. The presence of OTR subtypes was suggested by ligand-binding experiments (Chan et al 1993) but, to date, no subtypes have been identified by cross-species low-stringency genomic library screening.…”

Section: The Otr Gene and Its Transcriptional Regulationmentioning

confidence: 99%

Molecular regulation of the oxytocin receptor in peripheral organs

Kimura¹,

Saji²,

Nishimori³

et al. 2003

Journal of Molecular Endocrinology

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The oxytocin receptor belongs to the G-protein-coupled seven transmembrane receptor superfamily. Its main physiological role is regulating the contraction of uterine smooth muscle at parturition and the ejection of milk from the lactating breast. Oxytocin receptor expression is observed not only in the myometrium and mammary gland but also in the endometrium, decidua, ovary, testis, epididymis, vas deferens, thymus, heart and kidney, as well as in the brain. The expression profile shows a tissue-specific as well as a stage-specific pattern. The oxytocin receptor gene is a single-copy gene consisting of four exons and three introns, localized at 3p25-3p26·2 in the human chromosome. In transfection studies using a fusion construct containing the promoter region of the oxytocin receptor gene inserted in a reporter plasmid, neither proinflammatory cytokines nor oestrogen directly activate the gene. The nuclear fractions from up-regulated (term myometrium) and down-regulated (non-pregnant myometrium) tissues show differential patterns of protein binding to the 5′-flanking region, and a human homologue of chicken MafF has been cloned as a term-myometrium-specific oxytocin receptor modulator. The oxytocin receptor gene appears to be highly methylated. Methylation around intron 1 and in intron 3 might contribute to tissue-specific suppression of the gene. The oxytocin receptor is also regulated by desensitization, whose mechanism appears to involve loss of ligand-binding activity of the protein as well as suppression of the oxytocin receptor mRNA transcription. These findings taken together indicate that the oxytocin receptor is regulated in a very complicated manner, and the transcriptional regulatory elements critical for this regulation should be investigated further.

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Section: The Otr Gene and Its Transcriptional Regulationmentioning

confidence: 99%

Molecular regulation of the oxytocin receptor in peripheral organs

Kimura¹,

Saji²,

Nishimori³

et al. 2003

Journal of Molecular Endocrinology

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“…Pax3, which is expressed in precursors of limb muscles and regions of the central nervous system (Natoli et al 1997), is not appreciably methylated in any tissue or in sperm; the same is true of Oxtr [oxytocin receptor, expressed in myometrium, endometrium, mammary gland, and ovary (Kubota et al 1996)], and Hoxb4 [lung, kidney, testes; not present in liver, heart, or spleen (Gutman et al 1994)]. Complete demethylation in sperm and partial methylation in somatic tissues was observed only for Lep [leptin; expressed primarily in adipocytes (Hoggard et al 1997;Mason et al 1998), whereas complete methylation in sperm DNA and partial methylation in somatic tissues was observed for Mylc [alkaline myosin light chain; ventricular myocardium and slow skeletal muscle (Barton et al 1985)] and Prf1 [pore-forming protein; cytotoxic T lymphocytes and natural killer cells (Youn et al 1991;Lichtenheld et al 1995)].…”

Section: Methylation Status Of Promoters Of Tissue-specific Genes In mentioning

confidence: 99%

Cytosine methylation and mammalian development

Walsh

Bestor²

1999

Genes Dev.

372

241

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Programmed methylation and demethylation of regulatory sequences has been proposed to play a central role in vertebrate development. We report here that the methylation status of the 5 regions of a panel of tissue-specific genes could not be correlated with expression in tissues of fetal and newborn mice. Genes reported to be regulated by reversible methylation were not expressed ectopically or precociously in Dnmt1-deficient mouse embryos under conditions where demethylation caused biallelic expression of imprinted genes and activated transcription of endogenous retroviruses of the IAP class. These and other data suggest that the numerous published expression-methylation correlations may have described not a cause but a consequence of transcriptional activation. A model is proposed under which cytosine methylation represents a biochemical specialization of large genomes that participates in specialized biological functions such as allele-specific gene expression and the heritable transcriptional silencing of parasitic sequence elements, whereas cellular differentiation is controlled by conserved regulatory networks that do not depend on covalent modification of the genome.

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“…Although OXT is a strong uterotonin and is considered to drive parturition, the previous observations unexpectedly and clearly prove that OXT is not essential for labor in mice. In contrast, Oxtr mRNA expression in the uterus is up-regulated dramatically at term (11), uterine sensitivity to OXT increases just before parturition (12,13), and OXTR antagonists delay parturition in mice (14), suggesting an indispensable role for OXTR in mouse parturition. We therefore suspected that a redundant signaling through OXTR during parturition might compensate for the absence of OXT in Oxt Ϫ/Ϫ mice.…”

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confidence: 97%

Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice

Takayanagi

Yoshida

Bielsky

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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700

596

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The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene (Oxtr ؊/؊ ) and compared them with OXT-deficient (Oxt ؊/؊ ) mice. Oxtr ؊/؊ mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr ؊/؊ dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant Oxtr ؊/؊ males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult Oxtr ؊/؊ males also showed deficits in social discrimination and elevated aggressive behavior. Ligand Oxt ؊/؊ males from Oxt ؊/؊ dams, but not from Oxt ؉/؊ dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT͞OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior.lactation ͉ maternal behavior ͉ ultrasonic vocalization ͉ social discrimination ͉ aggressive behavior

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Structure and expression of the mouse oxytocin receptor gene

Cited by 87 publications

References 22 publications

Molecular regulation of the oxytocin receptor in peripheral organs

Molecular regulation of the oxytocin receptor in peripheral organs

Cytosine methylation and mammalian development

Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice

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