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

RNAi-mediated silencing of estrogen receptor in the ventromedial nucleus of hypothalamus abolishes female sexual behaviors
June 27, 2006
Sergei Musatov, Walter Chen, Donald W. Pfaff, Michael G. Kaplitt, and Sonoko Ogawa
PNAS
Estrogen receptor (ER) plays a major role in the regulation of neuroendocrine functions and behaviors by estrogens. Although the generation of ER knockout mice advanced our knowledge of ER functions, gene deletion using this method is global and potentially confounded by developmental consequences. To achieve a site-specific knockdown of ER in the normally developed adult brain, we have generated an adeno-associated virus vector expressing a small hairpin RNA targeting ER. After bilateral injection of this vector into the hypothalamic ventromedial nucleus in ovariectomized female mice, expression levels of ER 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 ER 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.
NOTE: This article is available in its entirety by paid subscription on the website.