Transgenic Rat Models for Breast Cancer Research

The laboratory rat is an important model for studying breast cancer due to the similarities in this disease between rats and humans. However, limited knowledge in manipulating the rat genome through transgenesis has prevented researchers from answering important questions in breast cancer research. We proposed to carry out detailed studies to optimize the variables in transgenic manipulation, to extend transgenic rat technology to inbred rat strains, and to develop rat embryo cryopreservation. We have evaluated multiple variables in the microinjection procedure and generated multiple transgenic rat lines which should be important for breast cancer research. We have developed an efficient cryopreservation procedure for rat embryos. Embryos from the outbred Sprague-Dawley and inbred Wistar-Furth and Copenhagen strains that possess unique characteristics for breast cancer research and multiple lines of transgenic rats that are useful for breast cancer research have been frozen. Lastly, due to the lack of rat embryonic stem cells that contribute to the germline, we have set up the technology for rat cloning, a technique which could allow researchers to generate germline mutations in cellular genes of the rat. This technology is critical for generating recessive mutations which are commonly described as the genetic basis for cancers.