The objective of this proposal is to study the regulation of genomic imprinting in mouse using the maternally expressed H19 gene as the experimental system. Genomic imprinting is the differential expression of alleles dependent upon the parental origin. It occurs in mammals and, as a consequence, both a maternal and a paternal copy of certain genes are required for normal development. In addition, imprinting is implicated in several human diseases, and the understanding of imprinting may facilitate the correction of these human diseases. Although several genes have been shown to be imprinted in both mice and humans, the mechanism by which parental identity is assigned is unclear. However, a strong candidate for the differential marking of alleles is methylation of cytosine residues in CpG dinucleotides. For H19, a paternal specific methylated sequence has been identified which is not required for transcription of H19.
The specific aim of this proposal is to determine the role of the paternally methylated H19 sequence by removing the sequence from the endogenous locus using homologous recombination and then studying the outcome in mice by analyzing H19 expression from the disrnpted allele in a parental-specific manner.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM018458-02
Application #
2634583
Study Section
Biological Sciences 2 (BIOL)
Project Start
1998-06-28
Project End
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104