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A Conditional Knockout Mouse Line of the Oxytocin Receptor

Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Dr. W. Scott Young, 3rd, Building 49, Room 5A51, 9000 Rockville Pike, Bethesda, Maryland 20892-4483. E-mail: wsy{at}mail.nih.gov.

Oxytocin plays important roles in reproductive physiology and various behaviors, including maternal behavior and social memory. Its receptor (Oxtr) is present in peripheral tissues and brain, so a conditional knockout (KO, –/–) would be useful to allow elimination of the receptor in specific sites at defined times. We created a line of mice in which loxP sites flank Oxtr coding sequence (floxed) enable Cre recombinase-mediated inactivation of the receptor. We expressed Cre recombinase in these mice either in all tissues (Oxtr^–/–) or the forebrain (Oxtr^FB/FB) using the Ca²⁺/calmodulin-dependent protein kinase II promoter. The latter KO has reduced Oxtr binding beginning 21–28 d postnatally, leading to prominent reductions in the lateral septum, hippocampus, and ventral pallidum. The medial amygdala is spared, and there is significant retention of binding within the olfactory bulb and nucleus and neocortex. We did not observe any deficits in the general health, sensorimotor functions, anxiety-like behaviors, or sucrose intake in either Oxtr^–/– or Oxtr^FB/FB mice. Females of both KO types deliver pups, but only the Oxtr^FB/FB mice are able to eject milk. Oxtr^–/– males show impaired social memory for familiar females, whereas the Oxtr^FB/FB males appear to recognize their species but not individuals. Our results confirm the importance of oxytocin in social recognition and demonstrate that spatial and temporal inactivation of the Oxtr will enable finer understanding of the physiological, behavioral, and developmental roles of the receptor.

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