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 #
5R37HD003132-21
Application #
3484911
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1980-06-01
Project End
1990-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
21
Fiscal Year
1989
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
Shi, Y P; Huang, T T; Carlson, E J et al. (1994) The mapping of transgenes by fluorescence in situ hybridization on G-banded mouse chromosomes. Mamm Genome 5:337-41
Miller, M W; Duhl, D M; Winkes, B M et al. (1994) The mouse lethal nonagouti (a(x)) mutation deletes the S-adenosylhomocysteine hydrolase (Ahcy) gene. EMBO J 13:1806-16
Epstein, C J (1993) The conceptual bases for the phenotypic mapping of conditions resulting from aneuploidy. Prog Clin Biol Res 384:1-18
Barsh, G S; Lovett, M; Epstein, C J (1990) Effects of the lethal yellow (Ay) mutation in mouse aggregation chimeras. Development 109:683-90
Barsh, G S; Epstein, C J (1989) The long-range restriction map surrounding the mouse agouti locus reveals a disparity between physical and genetic distances. Genomics 5:9-18
Barsh, G S; Epstein, C J (1989) Physical and genetic characterization of a 75-kilobase deletion associated with al, a recessive lethal allele at the mouse agouti locus. Genetics 121:811-8
Lovett, M; Epstein, C J (1987) The lethal yellow allele-associated provirus results in the production of chimeric viral-host RNAs. Proc Natl Acad Sci U S A 84:2853-7
Lovett, M; Cheng, Z Y; Lamela, E M et al. (1987) Molecular markers for the agouti coat color locus of the mouse. Genetics 115:747-54
Moreno, P A; Epstein, C J (1987) Enhanced susceptibility of mouse embryos heterozygous for oligosyndactyly (Os/+) to mitomycin C-induced skeletal abnormalities. Teratology 35:261-5
Epstein, C J (1986) Developmental genetics. Experientia 42:1117-28