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The Journal of Neuroscience, February 22, 2006, 26(8):2335-2342; doi:10.1523/JNEUROSCI.3743-05.2006

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Behavioral/Systems/Cognitive
Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice

Jessica D. Gatewood,¹ Aileen Wills,¹ Savera Shetty,¹ Jun Xu,² Arthur P. Arnold,² Paul S. Burgoyne,³ and Emilie F. Rissman¹

¹Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, ²Department of Physiological Science, University of California, Los Angeles, California 90095-1606, and ³Division of Developmental Genetics, National Institute for Medical Research, London NW7 1AA, United Kingdom

Correspondence should be addressed to Dr. Emilie F. Rissman, Department of Biochemistry and Molecular Genetics, P.O. Box 800733, University of Virginia, Charlottesville, VA 22908. Email: rissman{at}virginia.edu

Across human cultures and mammalian species, sex differences can be found in the expression of aggression and parental nurturing behaviors: males are typically more aggressive and less parental than females. These sex differences are primarily attributed to steroid hormone differences during development and/or adulthood, especially the higher levels of androgens experienced by males, which are caused ultimately by the presence of the testis-determining gene Sry on the Y chromosome. The potential for sex differences arising from the different complements of sex-linked genes in male and female cells has received little research attention. To directly test the hypothesis that social behaviors are influenced by differences in sex chromosome complement other than Sry, we used a transgenic mouse model in which gonadal sex and sex chromosome complement are uncoupled. We find that latency to exhibit aggression and one form of parental behavior, pup retrieval, can be influenced by both gonadal sex and sex chromosome complement. For both behaviors, females but not males with XX sex chromosomes differ from XY. We also measured vasopressin immunoreactivity in the lateral septum, which was higher in gonadal males than females, but also differed according to sex chromosome complement. These results imply that a gene(s) on the sex chromosomes (other than Sry) affects sex differences in brain and behavior. Identifying the specific X and/or Y genes involved will increase our understanding of normal and abnormal aggression and parental behavior, including behavioral abnormalities associated with mental illness.

Key words: sex chromosomes; vasopressin; aggression; parental behavior; Klinefelter syndrome; autism

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Received Sept. 4, 2005; revised Dec. 11, 2005; accepted Jan. 10, 2006.

Correspondence should be addressed to Dr. Emilie F. Rissman, Department of Biochemistry and Molecular Genetics, P.O. Box 800733, University of Virginia, Charlottesville, VA 22908. Email: rissman{at}virginia.edu

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