The applicant proposes to identify genes regulating early mammalian development. Progress in understanding mechanisms of later development has been rapid due to the conservation of gene function from Drosophila to mouse. However, gene targeting of mouse orthologues has been much less informative about the early events of cleavage, compaction, genesis of the extra-embryonic tissues, implantation, axis determination, gastrulation and neural induction. New strategies are necessary. A direct, genetic approach to identifying and characterizing early developmental genes is proposed. Firstly, deletions covering mouse chromosome 2 will be generated. These deletions will be created in embryonic stem (ES) cells where they will be mapped and the breakpoints cloned. The deletion chromosomes will be established in mice. Secondly, early developmental phenotypes will be characterized for the deletions we make, and for existing deletions of chromosome 2. Overlapping and nested deletions will be used to map genes, which are necessary for early development, from cleavage to neural induction. Lastly, a balancer chromosome 2 will be constructed. The balancer chromosome will permit efficient screening for chemically induced point mutations in the genes defined with the deletion chromosomes.
|Nadano, Daita; Sugihara, Kazuhiro; Paria, Bibhash C et al. (2002) Significant differences between mouse and human trophinins are revealed by their expression patterns and targeted disruption of mouse trophinin gene. Biol Reprod 66:313-21