Two genetic abnormalities affecting mammalian embryonic development will be investigated. Oligosyndactyly (Os) and dominant yellow (Ay) are both mutations which in the heterozygous form cause developmental abnormalities and in the homozygous form cause early embryonic death. Since the Ay mutation appears to be associated with the insertion of an ecotropic virus, the molecular basis of this mutation will be studied using probes to be developed against the Ay-associated proviral integration site and flanking host DNA sequences. The normal mRNA transcripts of the agouti locus will be identified in early embryos and the effects of the mutation assessed. Ay/Ay teratocarcinoma cell lines will be prepared and Ay/Ay equal to +/+ chimeras analyzed. Studies to correct the defect in Ay/Ay cells and to reproduce the defect in +/+ cells will be undertaken by microinjection of cloned DNA. The effect of dibutyryl cAMP on the ability of Ay/Ay embryos to hatch in vitro will be assessed. The relationship between the heterozygous manifestations of Os and the mitotic defect identified in Os/Os embryos will be analyzed. Cellular proliferation in Os/+ egg cylinders and limb buds will be determined, and the effect of the calcium ionophone, A23187, assessed.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HD003132-22
Application #
3484912
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1980-06-01
Project End
1990-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
22
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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