Meeting Abstract

36.5  Thursday, Jan. 5  Disruption of Developmental & Epigenetic Programs in Peromyscus Hybrids VRANA, P.B.; University of South Carolina

We use North American rodents of the genus Peromyscus (deer mice) to study the effects of natural genetic variation on epigenetic regulation and development. The P. maniculatus species complex is particularly widespread and varied, consisting of a series of partially reproductively isolated populations. For example, crosses between P. maniculatus (BW), and P. polionotus (PO), produce dramatic parent-of-origin effects on growth and development. BW females mated to PO males (bw x po) results in growth-retarded offspring but apparently healthy offspring. In contrast, PO females mated to BW males (PO x BW) produce overgrown but severely dysmorphic conceptuses. The rare PO x BW litters which reach parturition harbor fatal defects (e.g. hemorrhaging) and/or are unable to pass through the birth canal, resulting in maternal lethality. The placenta is particularly affected in both cases; ~ 10% of PO x BW conceptuses consist only of extra-embryonic tissues. BrdU and TUNEL studies show that both proliferation and cell death are altered. Expression of imprinted genes and DNA methylation at associated regulatory regions is perturbed in the PO x BW hybrids. Studies on the etiology of the placental phenotypes indicate lineage misallocation. For example, expression of Cdx2, a trophoblast stem cell marker, drops over time in PO x BW placentas (relative to parental strains and bw x po hybrids). At the same time, the PO x BW placentas re-express the pluripotency marker Oct4 at high levels. Thus both differentiation and stem cell numbers and/or maintenance appear compromised. Nascent analysis of comparative transcriptome data will also be discussed; among these are species differences in expression of apoptosis-related loci.