Development of a Mouse Model for Determination of the Role of the Catechol Metabolites of Estradiol in Mammary Tumorigenesis
Abstract
The purpose of the proposed research is to develop a catechol-o-methyltransferase knockout (COMTKO)-estrogen receptor/Wnt-1 (ERKO/Wnt-1)-mouse model for use in studies on the role of estrogen catechol metabolites in mammary tumorigenesis. The scope of the project involves: 1) Through genetic crossing, introduce the COMT KO genotype into the ERKO/Wnt-1 mice; 2) Initiate studies to determine the effects of the absence of COMT on estrogen catechol metabolite, glutathione-estrogen quinone adduct levels (which reflect oxidative metabolism of estrogen catechol to estrogen quinones), oxidative DNA damage levels, mammary gland development and tumorigenesis in the resulting COMTKO/ERKO/Wnt-1 female mice. ERKO/Wnt-1 mice were obtained after notification of award; COMTKO mice were on-hand. However, unanticipated difficulties were encountered. The COMTKO mice went through a period where their breeding stopped. Additional breeding pairs were obtained from the originator of the strain at Rockefeller University. These mice began breeding and at that point, the first aim could proceed, although we were already about 6 months behind given the time required to obtain additional breeding pairs, time in quarantine, and time for them to adapt and produce off-spring for the desired crosses. As detailed in the progress report, breeding is now proceeding. The project period has been extended 1 year to 20 August, 2005.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA431900
Entities
People
- James D. Yager
Organizations
- Johns Hopkins University