Estrogen Receptor Alpha G525L Knock-In-Mice
Abstract
We have developed a knock-in mouse model with a mutation (glycine 525 to leucine, G525L) in estrogen receptor alpha (ERalpha) that permits exogenous regulation of its ligand-induced signaling pathways, while not affecting ligand-independent signaling. This ligand-binding pocket mutation significantly reduces ERalpha response to endogenous estrogens but not to the synthetic nonsteroidal estrogen diethylstilbestrol (DES). Therefore, ERalpha signaling pathways can be regulated in these mice through DES administration or withdrawal. Female mutant G525L ERalpha homozygous mice had immature and hypoplastic uterine and vaginal tissues and only developed rudimentary mammary gland ductal trees. Homozygous ovarian tissues had a hyperplasic stroma and no corpora lutea. In addition, some of the homozygous ovaries contained large, hemorrhagic, cystic follices. Cyst development increased with age. Homozygous animals had higher estrogen (E) and luteinizing hormone (LH) serum levels than their wild type and heterozygous littermates. Homozygous animals were also significantly larger than their wild type and heterozygous littermates. This was partly due to an increase in gonadel and mammary fat pad weight. Further analysis of this knock-in mouse model, including examination of non-reproductive tissues and uterotrophic assays with E, DES, and epidermal growth factor (EGF), will provide valuable information about the role of ligand-induced and ligand-independent ER signaling in development and carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2006
- Accession Number
- ADA452866
Entities
People
- Kerstin W. Sinkevicius
Organizations
- University of Chicago