Altered hematopoiesis, behavior, and sexual function in μ opioid receptor-deficient mice

Mingting Tian, Hal Broxmeyer, Yi Fan, Zhennan Lai, Shengwen Zhang, Susan Aronica, Scott Cooper, Robert Bigsby, Rosemary Steinmetz, Sandra J. Engle, Anton Mestek, Jonathan D. Pollock, Michael N. Lehman, Heiko T. Jansen, Moym Ying, Peter J. Stambrook, Jay A. Tischfield, Lei Yu

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

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 granylocyte-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.

Original languageEnglish
Pages (from-to)1517-1522
Number of pages6
JournalJournal of Experimental Medicine
Volume185
Issue number8
DOIs
StatePublished - Apr 21 1997

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Hematopoiesis
Opioid Receptors
Sexual Behavior
Homozygote
Locomotion
Morphine
Opioid Analgesics
Biological Phenomena
Pain
Litter Size
Erythroid Precursor Cells
Sperm Count
Sperm Motility
Homologous Recombination
Narcotics
Heroin
Genes
Spleen
Bone Marrow
Macrophages

ASJC Scopus subject areas

  • Immunology

Cite this

Altered hematopoiesis, behavior, and sexual function in μ opioid receptor-deficient mice. / Tian, Mingting; Broxmeyer, Hal; Fan, Yi; Lai, Zhennan; Zhang, Shengwen; Aronica, Susan; Cooper, Scott; Bigsby, Robert; Steinmetz, Rosemary; Engle, Sandra J.; Mestek, Anton; Pollock, Jonathan D.; Lehman, Michael N.; Jansen, Heiko T.; Ying, Moym; Stambrook, Peter J.; Tischfield, Jay A.; Yu, Lei.

In: Journal of Experimental Medicine, Vol. 185, No. 8, 21.04.1997, p. 1517-1522.

Research output: Contribution to journalArticle

Tian, M, Broxmeyer, H, Fan, Y, Lai, Z, Zhang, S, Aronica, S, Cooper, S, Bigsby, R, Steinmetz, R, Engle, SJ, Mestek, A, Pollock, JD, Lehman, MN, Jansen, HT, Ying, M, Stambrook, PJ, Tischfield, JA & Yu, L 1997, 'Altered hematopoiesis, behavior, and sexual function in μ opioid receptor-deficient mice', Journal of Experimental Medicine, vol. 185, no. 8, pp. 1517-1522. https://doi.org/10.1084/jem.185.8.1517
Tian, Mingting ; Broxmeyer, Hal ; Fan, Yi ; Lai, Zhennan ; Zhang, Shengwen ; Aronica, Susan ; Cooper, Scott ; Bigsby, Robert ; Steinmetz, Rosemary ; Engle, Sandra J. ; Mestek, Anton ; Pollock, Jonathan D. ; Lehman, Michael N. ; Jansen, Heiko T. ; Ying, Moym ; Stambrook, Peter J. ; Tischfield, Jay A. ; Yu, Lei. / Altered hematopoiesis, behavior, and sexual function in μ opioid receptor-deficient mice. In: Journal of Experimental Medicine. 1997 ; Vol. 185, No. 8. pp. 1517-1522.
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