International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Plenary Presentations * Oral Presentations *
Poster Presentations: Complex Genetics and Disease Modifiers * Developmental Genetics * Functional Genomics * Gene Discovery * Genetic Manipulations to Alter Gene Function * Mouse Models: Human Disease and Pharmacogenetics * Sequence Annotation and Comparative Analysis of Genomes *
Attendees * Sponsors * Table of Contents * Photographs * Awards

POSTER 137 - DEVELOPMENTAL PROFILE OF DNA METHYLATION AND GENE EXPRESSION AT THE H19 LOCUS IN MICE LACKING SEQUENCE REQUIRED FOR GENOMIC IMPRINTING

J Thorvaldsen
University of Pennsylvania School of Medicine

1) Yang G, 1) Nguyen S, 2) Magnuson M, 3) Bartolomei M
1) University of Pennsylvania School of Medicine, 2)Vanderbilt University Medical Center, 3) HHMI and University of Pennsylvania School of Medicine

The 2 kb differentially methylated domain (DMD) 5’ of H19 is exclusively methylated on the paternal allele throughout development and is required for H19 and Igf2 imprinting. In mice harboring a 1.6 kb deletion of the DMD (DDMD) or a 3.8 kb deletion spanning the DMD (D3.8kb-5’H19), loss of H19 and Igf2  imprinting is detected in all neonatal tissues (G&D 12:3693, MCB 22:2450). In addition, the DMD is required for full expression of H19 and Igf2. Nevertheless, DMD sequence that remains in the DDMD mice,  acquires slightly more methylation on the paternal allele than on the maternal allele, indicating that some parental-specific identity is maintained that does not result in differences in parental-specific expression. We are currently investigating allele-specific DNA methylation and gene expression patterns at the H19 locus in the DDMD and the D3.8kb-5’H19 mice in early stages of development to determine when loss of H19 and Igf2  imprinting occurs. We have also generated a conditional (floxed) targeted allele of the 1.6 kb DMD sequence. Removal of this sequence in neonatal liver results in loss of Igf2  but not H19 imprinting. Thus, the DMD is required for maintenance of Igf2  but not for H19 imprinting in non-dividing tissues. In summary, analysis of the DMD deletions throughout development will be important to determine the sequence requirements and mechanism of imprinting at the H19 locus.