The long-range goal of the proposed studies is to understand the function of homeobox-containing genes in mammalian limb development. The applicant has devised two specific aims toward that end.
The first aim will be to use gene targeting in mouse embryo- derived stem cells (ES cells) to generate mouse mutants with targeted disruptions in each of 11 homeobox- containing (Hox) genes of interest in three linkage groups (including hoxa-10, -11, -13; hoxc-10, -11, -12, -13; hoxd- 10, -11, -12, & -13). The limbs from each of these loss-of-function mutants will be examined for defects to define the zone of influence of each of the genes. The applicant anticipates that through systematic analyses of the phenotypes of all these mutants, some logic will emerge regarding the relationships between these genes and their role in limb patterning.
The second aim i s to determine how these genes interact in regulating limb development.Additional gene targeting and cross-breeding will be used to combine appropriate single mutations to generate double and triple mutants. The applicant will then analyze the phenotypic outcome of combining the mutations both within and across linkage groups. In addition, the influence exerted by mutation of one hox gene on the expression of another will be examined by introducing the lacZ reporter gene into the latter.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD030701-01A2
Application #
2203034
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1994-12-15
Project End
1998-11-30
Budget Start
1994-12-15
Budget End
1995-11-30
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Utah
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112