Development of a Mouse Model for Determination of the Role of the Catechol Metabolites of Estradiol in Mammary Tumorigenesis

摘要

The goal was to develop a catechol-o-methyltransferase knockout (COMTKO)-estrogen receptorlwnt-I (ERKOANnt-I) mouse model to study the role of estrogen catechol metabolites in mammary tumorigenesis. The aims were: Through a complex genetic crossing, introduce the COMTKO genotype into the ERCOIWnt-I mice; Initiate studies to determine the effects of the absence of COMT on several biochemical end points and on mammary gland development and tumorigenesis in the resulting COMTKO/ERCOlWnt-1 female mice. ERKOlWnt-1 mice were obtained after notification of award; COMTKO mice were on-hand. Unanticipated difficulties were encountered. Additional breeding pairs were obtained and successful breeding began. Because of the delay, a 1 year extension of the project to 20 August, 2005 without additional funds was requested and granted. Appropriate breeding pairs have now been developed and breeding is ongoing to generate the mice needed for the study.