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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD037934-03
Application #
6521218
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Moody, Sally Ann
Project Start
2000-04-01
Project End
2005-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
3
Fiscal Year
2002
Total Cost
$275,400
Indirect Cost
Name
Case Western Reserve University
Department
Genetics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106