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The Journal of Neuroscience, July 9, 2008, 28(28):7137-7142; doi:10.1523/JNEUROSCI.1345-08.2008

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Behavioral/Systems/Cognitive
Mecp2 Organizes Juvenile Social Behavior in a Sex-Specific Manner

Joseph R. Kurian,¹ Meaghan E. Bychowski,² Robin M. Forbes-Lorman,¹ Catherine J. Auger,^1,2 and Anthony P. Auger^1,2

¹Department of Psychology, and ²Neuroscience Training Program, University of Wisconsin–Madison, Madison, Wisconsin 53706

Correspondence should be addressed to Anthony P. Auger, Department of Psychology, University of Wisconsin–Madison, 1202 West Johnson Street, Madison, WI 53706. Email: apauger{at}wisc.edu

Methyl-CpG-binding protein 2 (MeCP2) binds methylated DNA and recruits corepressor proteins to modify chromatin and alter gene transcription. Mutations of the MECP2 gene can cause Rett syndrome, whereas subtle reductions of MeCP2 expression may be associated with male-dominated social and neurodevelopmental disorders. We report that transiently decreased amygdala Mecp2 expression during a sensitive period of brain sexual differentiation disrupts the organization of sex differences in juvenile social play behavior. Interestingly, neonatal treatment with Mecp2 small interfering RNA within the developing amygdala reduced juvenile social play behavior in males but not females. Reduced Mecp2 expression did not change juvenile sociability or anxiety-like behavior, suggesting that this disruption is associated with subtle behavioral modification. This suggests that Mecp2 may have an overlooked role in the organization of sexually dimorphic behaviors and that male juvenile behavior is particularly sensitive to Mecp2 disruption during this period of development.

Key words: Mecp2; siRNA; amygdala; sex difference; behavior; epigenetic

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Received Dec. 7, 2007; revised May 28, 2008; accepted May 28, 2008.

Correspondence should be addressed to Anthony P. Auger, Department of Psychology, University of Wisconsin–Madison, 1202 West Johnson Street, Madison, WI 53706. Email: apauger{at}wisc.edu

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