Retroelement demethylation associated with abnormal placentation in Mus musculus x Mus caroli hybrids

Biology of Reproduction
Judith D BrownRachel J O'Neill

Abstract

The proper functioning of the placenta requires specific patterns of methylation and the appropriate regulation of retroelements, some of which have been co-opted by the genome for placental-specific gene expression. Our inquiry was initiated to determine the causes of the placental defects observed in crosses between two species of mouse, Mus musculus and Mus caroli. M. musculus × M. caroli fetuses are rarely carried to term, possibly as a result of genomic incompatibility in the placenta. Taking into account that placental dysplasia is observed in Peromyscus and other Mus hybrids, and that endogenous retroviruses are expressed in the placental transcriptome, we hypothesized that these placental defects could result, in part, from failure of the genome defense mechanism, DNA methylation, to regulate the expression of retroelements. Hybrid M. musculus × M. caroli embryos were produced by artificial insemination, and dysplastic placentas were subjected to microarray and methylation screens. Aberrant overexpression of an X-linked Mus retroelement in these hybrid placentas is consistent with local demethylation of this retroelement, concomitant with genome instability, disruption of gene regulatory pathways, and dysgenesis. We pro...Continue Reading

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Methods Mentioned

BETA
PCR
chips
DNA-Chip
three hybrid
Chip
transfection

Related Concepts

Chimera Organism
Hybridization, Intraspecies
Mice, Inbred Strains
Hemochorial Placentation
Mobile Dispersed Genetic Elements
DNA Methylation
Genomic Stability
Karyotype
Defense Mechanisms
Embryo

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