Format

Send to:

Choose Destination
See comment in PubMed Commons below
Genetics. 2010 Nov;186(3):917-27. doi: 10.1534/genetics.110.118802. Epub 2010 Aug 16.

A genomic imprinting defect in mice traced to a single gene.

Author information

  • 1Division of Biology, Beckman Research Institute, City of Hope National Medical Center, Duarte, California 91010, USA.

Abstract

Mammalian androgenones have two paternally or sperm-derived genomes. In mice (Mus musculus) they die at peri-implantation due to the misexpression of imprinted genes-the genes that are expressed monoallelically according to the parent of origin. The misexpressions involved are poorly defined. To gain further insight, we examined the causes of midgestation death of embryos with paternal duplication (PatDp) of distal chromosome 7 (dist7), a region replete with imprinted genes. PatDp(dist7) embryos have a similar phenotype to mice with a knockout of a maternally expressed imprinted gene, Ascl2 [achaete-scute complex homolog-like 2 (Drosophila)], and their death at midgestation could result from two inactive paternal copies of this gene. However, other dist7 misexpressions could duplicate this phenotype, and the potential epistatic load is undefined. We show that an Ascl2 transgene is able to promote the development of PatDp(dist7) embryos to term, providing strong evidence that Ascl2 is the only imprinted gene in the genome for which PatDp results in early embryonic death. While some of the defects in perinatal transgenic PatDp(dist7) fetuses were consistent with known misexpressions of dist7 imprinted genes, the overall phenotype indicates a role for additional undefined misexpressions of imprinted genes. This study provides implications for the human imprinting-related fetal overgrowth disorder, Beckwith-Wiedemann syndrome.

PMID:
20713691
[PubMed - indexed for MEDLINE]
PMCID:
PMC2975296
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk