One in two hundred children is born with limb deformities. An under- standing of the teleology of these defects, whether induced by taratogens, caused from a stochastic dysfunction of the developmental program, or the result of congenital defects, will require an under- standing of the normal process of limb development. Many of the genes that are suspected of mediating the formation of the limbs are now being identified. Particularly prominent among these genes is the set of Hox genes that may be required to specify the positional information needed for the establishment of the correct set of limb cartilages and bones. Gene targeting in mouse embryo-derived stem cells provides the means for generating mice with disruptions in each of these genes. The goal of this grant is to use gene targeting to undertake a systematic analysis of this gene complex and thereby directly establish the role of each of these genes in limb development. Not only will the phenotypic consequences of disrupting any particular gene be determined, but also through epistasis and molecular genetic analysis, it is hoped that insight will be gained as to how this set of genes functions as a network to determine the overall three-dimensional structure of the limb.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD030701-09
Application #
6625252
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Javois, Lorette Claire
Project Start
1994-12-15
Project End
2003-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
9
Fiscal Year
2003
Total Cost
$362,357
Indirect Cost
Name
University of Utah
Department
Genetics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112