Targeted Reduction of Oxytocin Expression Provides Insights into its Physiological Roles

  • W. Scott YoungIII
  • Emily Shepard
  • A. Courtney DeVries
  • Andreas Zimmer
  • Mary E. LaMarca
  • Edward I. Ginns
  • Janet Amico
  • Randy J. Nelson
  • Lothar Hennighausen
  • Kay-Uwe Wagner
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 449)

Abstract

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of thesefunctions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 hours without milk in their stomachs. OT injection into the dams or rescue with the rat OT gene restores the milk ejection in response to suckling. OT is also needed for post-partum alveolar proliferation. These results indicate an absolute requirement for oxytocin for successful milk ejection, but not for mating, parturition and milk production, in mice. Furthermore, homozygous mutant mice show reduced aggression in some tests.

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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • W. Scott YoungIII
    • 1
  • Emily Shepard
    • 1
  • A. Courtney DeVries
    • 2
  • Andreas Zimmer
    • 3
  • Mary E. LaMarca
    • 4
  • Edward I. Ginns
    • 4
  • Janet Amico
    • 5
  • Randy J. Nelson
    • 6
  • Lothar Hennighausen
    • 7
  • Kay-Uwe Wagner
    • 7
  1. 1.Laboratory of Cellular and Molecular RegulationNational Institute of Mental HealthBethesdaUSA
  2. 2.Laboratory of Behavioral PharmacologyNational Institute of Mental HealthBethesdaUSA
  3. 3.Section on GeneticsNational Institute of Mental HealthBethesdaUSA
  4. 4.Clinical Neuroscience BranchNational Institute of Mental HealthBethesdaUSA
  5. 5.Division of Endocrinology and MetabolismUniversity of Pittsburgh, School of Medicine and VA Medical CenterPittsburghUSA
  6. 6.Departments of Psychology and NeuroscienceThe Johns Hopkins UniversityBaltimoreUSA
  7. 7.Laboratory of Biochemistry and MetabolismNational Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of HealthBethesdaUSA

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