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 54 - MOLECULAR AND HISTOLOGICAL CHARACTERIZATION OF MURINE EPIDERMAL GROWTH FACTOR RECEPTOR NULL PLACENTAE

M Hovick
Department of Genetics

Hovick M, Strunk KE, Clore J, Threadgill DW
University of North Carolina-Chapel Hill, Department of Genetics

The epidermal growth factor receptor (Egfr) is a 170-kilodalton protein containing a ligand binding, single transmembrane and cytoplasmic tyrosine kinase domain.  Upon ligand binding, Egfr activates intracellular signaling cascades to effect cell growth and/or differentiation.  The Egfr is normally expressed in a number of adult tissues and misexpressed in a variety of human cancers of epithelial origin.  Mice homozygous for a null allele of Egfr (Egfrtm1Mag) display variable phenotypes depending on genetic background.  A reduction in the number of spongiotrophoblast cells has been observed in placentae of Egfr null homozygotes on all genetic backgrounds tested.  In order to determine the molecular mechanism behind the placental defects, the levels of proliferation were quantified in both Egfr null and wild-type placentae at e10.5, e13.5 and e18.5.  At e10.5 BrdU incorporation was reduced in the Egfr null placenta relative to wild-type; however, PCNA staining was increased in the Egfr null placenta.  Since BrdU specifically labels cells actively undergoing S phase of the cell cycle and PCNA is detected during S, G2 and M phases, we hypothesize that the Egfr null placenta has an aberrant cell cycle during early placental development.  Equivalent PCNA levels are detected at the late gestation e18.5 time point in both wild-type and null placentae, suggesting that the late gestation Egfr null placenta has a normal cell cycle.  Further molecular analyses and genetic crosses are underway using p53 and Rb null alleles to test the role of cell cycle progression on the Egfr null phenotype.