The long term goal of this proposal is to develop a scheme for identifying and characterizing mammalian genes which cause developmental abnormalities. In the course of studying chlorambucil-induced mutagenesis in the mouse, we have found that chlorambucil (CHL) is a very efficient inducer of recessive visible mutations. Because CHL induces gross chromosomal abnormalities (deletions, translocations, etc.) instead of point mutations, the mutations caused by this drug can be easily mapped and characterized. We would like to use these mutations to positionally clone and characterize mammalian genes which cause developmental abnormalities. In this grant proposal, we would like to establish the parameters of the CHL mutagenesis system as well as produce a new series of recessive visible and developmental mutations in the mouse.
Our specific aims are: (1) to determine the most efficient system for producing CHL mutations in mice, (2) to produce dominant and recessive visible mutations affecting development, (3) to map new CHL-induced mutations to specific chromosomal regions, and (4) to further characterize the usefulness of CHL as an inducer of specific mutations.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050283-02
Application #
2188000
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1994-03-01
Project End
1998-02-28
Budget Start
1995-03-01
Budget End
1996-02-29
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Wadsworth Center
Department
Type
DUNS #
110521739
City
Menands
State
NY
Country
United States
Zip Code
12204
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Kuster, J E; Guarnieri, M H; Ault, J G et al. (1997) IAP insertion in the murine LamB3 gene results in junctional epidermolysis bullosa. Mamm Genome 8:673-81

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