The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/4/1517/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 8, April 21, 1997 1517-1522

Brief Definitive Reports

Altered Hematopoiesis, Behavior, and Sexual Function in µ Opioid Receptor–deficient Mice

Mingting Tian*, Hal E. Broxmeyer{ddagger},||,¶, Yi Fan*, Zhennan Lai*, Shengwen Zhang*, Susan Aronica{ddagger},||,¶, Scott Cooper{ddagger},||,¶, 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*, and Lei Yu*,§

From the * Department of Medical and Molecular Genetics, {ddagger} 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

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.

Address correspondence to Lei Yu, Department of Medical and Molecular Genetics, Indiana University School of Medicine, 975 West Walnut St., Indianapolis, IN 46202.


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