RNAi-mediated silencing of estrogen receptor {alpha} in the ventromedial nucleus of hypothalamus abolishes female sexual behaviors.

Publication Type	Academic Article
Authors	Musatov S, Chen W, Pfaff D, Kaplitt M, Ogawa S
Journal	Proc Natl Acad Sci U S A
Volume	103
Issue	27
Pagination	10456-10460
Date Published	06/27/2006
ISSN	0027-8424
Keywords	Estrogen Receptor alpha, RNA Interference, Sexual Behavior, Ventromedial Hypothalamic Nucleus
Abstract	Estrogen receptor alpha (ERalpha) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although the generation of ERalpha knockout mice advanced our knowledge of ERalpha functions, gene deletion using this method is global and potentially confounded by developmental consequences. To achieve a site-specific knockdown of ERalpha in the normally developed adult brain, we have generated an adeno-associated virus vector expressing a small hairpin RNA targeting ERalpha. After bilateral injection of this vector into the hypothalamic ventromedial nucleus in ovariectomized female mice, expression levels of ERalpha as well as the estrogen-inducible progesterone receptor were profoundly reduced despite the continued presence of this receptor elsewhere in the brain. Functionally, silencing of ERalpha in the ventromedial nucleus abolished female proceptive and receptive sexual behaviors while enhancing rejection behavior. These results provide evidence that adeno-associated virus-mediated long-term knockdown of genes can be used to delineate their effects on complex behaviors in discrete brain regions.
DOI	10.1073/pnas.0603045103
PubMed ID	16803960
PubMed Central ID	PMC1502479