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An estrogen receptor repressor induces cataract formation in transgenic mice.

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An estrogen receptor repressor induces cataract formation in transgenic mice.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Korach, Kenneth S. Schoen, Timothy J. Couse, John F. Chader, Gerald J. Chan, Chi-chao Davis, Vicki L.
Description	Author Affiliation: Davis VL ( Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. vicki.davis@cshs.org);
Abstract	Despite the high prevalence of age-related cataracts, there are currently no known therapies to delay or prevent their occurrence. Studies in humans and rodent models suggest that estrogen may provide protection against age-related cataracts. The discovery of ocular estrogen receptors (ERs) indicates that estrogen protection may result from direct interactions with its receptors in the eye, instead an indirect consequence from effects on another tissue. Studies in our transgenic mouse model validate the concept that estrogen is beneficial for the eye. These mice express ER Delta , a dominant-negative form of ER alpha that inhibits ER alpha function. In the ER Delta 3 transgenic mice, cortical cataracts spontaneously form in ER Delta 3 females after puberty and progress with age. The cataracts initiate in the equatorial region of the lens where the epithelial cells differentiate into elongating fiber cells. Cataract formation can be prevented if the females are ovariectomized before, but not after, sexual maturity. Both male and female ER Delta 3 mice develop cataracts after neonatal treatment with the potent estrogen diethylstilbestrol (DES). The incidence of spontaneous and DES-induced cataracts in ER Delta 3 mice is 100%, yet these cataracts are absent from the wild-type mice. These data suggest that repression of estrogen action induces cortical cataract formation because estrogen is required to activate the ER Delta 3 repressor. Evidence of DES-induced cataracts in the ER Delta 3 males as well as the females suggests that estrogen is important in lens physiology in both sexes. The ER Delta 3 mice provide a powerful model for assessing the role of estrogen in maintaining the transparency of the lens.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	14
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cataract Etiology Receptors, Estrogen Antagonists & Inhibitors Repressor Proteins Metabolism Animals Animals, Newborn Genetics Pathology Diethylstilbestrol Toxicity Estrogen Receptor Alpha Mice Mice, Transgenic Models, Biological Ovariectomy Sexual Maturation Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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