The μ opioid receptor is thought to be the cellular target of opioid narcotics such as morphine and heroin, mediating their effects in both pain relief and euphoria. Its involvement is also implicated in a range of diverse biological processes. Using a mouse model in which the receptor gene was disrupted by targeted homologous recombination, we explored the involvement of this receptor in a number of physiological functions. Mice homozygous for the disrupted gene developed normally, but their motor function was altered. Drug-naive homozygotes displayed reduced locomotor activity, and morphine did not induce changes in locomotor activity observed in wild-type mice. Unexpectedly, lack of a functional receptor resulted in changes in both the host defense system and the reproductive system. We observed increased proliferation of granulocyte-macrophage, erythroid, and multipotential progenitor cells in both bone marrow and spleen, indicating a link between hematopoiesis and the opioid system, both of which are stress-responsive systems. Unexpected changes in sexual function in male homozygotes were also observed, as shown by reduced mating activity, a decrease in sperm count and motility, and smaller litter size. Taken together, these results suggest a novel role of the μ opioid receptor in hematopoiesis and reproductive physiology, in addition to its known involvement in pain relief.
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21 April 1997
Brief Definitive Report|
April 21 1997
Altered Hematopoiesis, Behavior, and Sexual Function in μ Opioid Receptor–deficient Mice
Mingting Tian,
Mingting Tian
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Hal E. Broxmeyer,
Hal E. Broxmeyer
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Yi Fan,
Yi Fan
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Zhennan Lai,
Zhennan Lai
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Shengwen Zhang,
Shengwen Zhang
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Susan Aronica,
Susan Aronica
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Scott Cooper,
Scott Cooper
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Robert M. Bigsby,
Robert M. Bigsby
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Rosemary Steinmetz,
Rosemary Steinmetz
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Sandra J. Engle,
Sandra J. Engle
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Anton Mestek,
Anton Mestek
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Jonathan D. Pollock,
Jonathan D. Pollock
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Michael N. Lehman,
Michael N. Lehman
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Heiko T. Jansen,
Heiko T. Jansen
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Moyin Ying,
Moyin Ying
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Peter J. Stambrook,
Peter J. Stambrook
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Jay A. Tischfield,
Jay A. Tischfield
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Lei Yu
Lei Yu
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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Mingting Tian
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Hal E. Broxmeyer
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Yi Fan
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Zhennan Lai
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Shengwen Zhang
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Susan Aronica
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Scott Cooper
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Robert M. Bigsby
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Rosemary Steinmetz
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Sandra J. Engle
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Anton Mestek
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Jonathan D. Pollock
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Michael N. Lehman
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Heiko T. Jansen
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Moyin Ying
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Peter J. Stambrook
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Jay A. Tischfield
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Lei Yu
From the *Department of Medical and Molecular Genetics, ‡Department of Microbiology and Immunology, §Department of Physiology and Biophysics, ‖Department of Medicine, and ¶Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202; and the **Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
Address correspondence to Lei Yu, Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut St., Indianapolis, IN 46202.
Received:
February 10 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (8): 1517–1522.
Article history
Received:
February 10 1997
Citation
Mingting Tian, Hal E. Broxmeyer, Yi Fan, Zhennan Lai, Shengwen Zhang, Susan Aronica, Scott Cooper, Robert M. Bigsby, Rosemary Steinmetz, Sandra J. Engle, Anton Mestek, Jonathan D. Pollock, Michael N. Lehman, Heiko T. Jansen, Moyin Ying, Peter J. Stambrook, Jay A. Tischfield, Lei Yu; Altered Hematopoiesis, Behavior, and Sexual Function in μ Opioid Receptor–deficient Mice. J Exp Med 21 April 1997; 185 (8): 1517–1522. doi: https://doi.org/10.1084/jem.185.8.1517
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