Although failure of placental development or function is one of the most common causes of embryonic death during gestation in humans and other vertebrates, little is known about the genetic regulation of extraembryonic development. One functional unit identified in the albino-deletion complex on chromosome 7 which is important during early postimplantation in the mouse is the extraembryonic ectoderm development (exed) region. Embryos homozygous for deletions removing this region display abnormalities of extraembryonic structures, particularly in the extraembryonic ectoderm which is severely reduced and pyknotic. Development of these embryos is truncated and they die around embryonic day 7.5-8.0. It is unknown whether the primary effect is on extraembryonic development since the embryonic ectoderm is also small. The role of exed will be clarified by rescuing either the extraembryonic or embryonic portion of the phenotype with tetraploid-diploid chimeras. Deletion complementation analyses have demonstrated that loss of a 20 kb regiori is necessary for the phenotype. However it is not known whether this region is sufficient to cause the phenotype when deleted, or whether other genes removed outside the 20 kb region also contribute to the exed phenotype. To clarify this issue, the 20 kb region will be deleted using the Cre-loxP system with targeted homologous recombination. Finally, exed will be positionally cloned, with the search beginning in the 20 kb region.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
3F32HD008268-02S1
Application #
2884767
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Moody, Sally Ann
Project Start
1998-08-01
Project End
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Genetics
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106