Mouse Developmental Genetics
The embryonic development of the mouse is highly complex and very organized, but remarkably little is known about genes (of which there must be many) involved in determining and controlling tissue fates, differentiation, general morphogenetic processes and growth control.
We have been involved in the development of a system which has become important for elucidating the developmental genetics of the mouse and facilitates the production of mouse models of human genetic disease.
This system involves the isolation of stem cell lines from preimplantation embryos. These stem cells are amenable to genetic modification while in culture and they can be returned to host embryos which will develop to term in a foster mother. The anima ls born are mosaic in all tissues and breeding analysis confirms that cells propagated in tissue culture are incorporated into the germ line of these mice.
In Dr. Bradley's laboratory these cells are being used as a route into the germ line. This route can accomplish many genetic modifications of the mouse genome that could not be realized with other techniques. Gene targeting techniques are being perform ed on these cells to mutagenize genes in order to ascertain their relevance in development and growth control.
Currently we are developing various technologies to use the knockout mouse as an assay to clone tumor suppressor genes. Towards this goal, we have recently developed a technique to make mice which are missing hundreds of genes. We are currently focusing on identifying genes which are mutated in breast cancer.