Peg3 mutational effects on reproduction and placenta-specific gene families. Mus musculus

Peg3 (paternally expressed gene 3) is an imprinted gene encoding a DNA-binding protein. This gene plays important roles in controlling fetal growth rates and nurturing behaviors. In the current study, a new mutant mouse model has been generated to further characterize the functions of this DNA-binding protein. Besides known phenotypes, this new mutant model also revealed potential roles of Peg3 in mammalian reproduction. Female heterozygotes produce a much smaller number of mature oocytes than the wild-type littermates, resulting in reduced litter sizes. According to genome-wide expression analyses, several placenta-specific gene families are de-repressed in the brain of Peg3 heterozygous embryos, including prolactin, cathepsin and carcinoembryonic antigen cell adhesion molecule (Ceacam) families. The observed de-repression is more pronounced in females than in males. The de-repression of several members of these gene families is observed even in the adult brain, suggesting potential defects in epigenetic setting of the placenta-specific gene families in the Peg3 mutants. Overall, these results indicate that Peg3 likely controls the transcription of several placenta-specific gene families, and further suggest that this predicted transcriptional control by Peg3 might be mediated through unknown epigenetic mechanisms. Overall design: Mouse Breeding Two different types of heterozygotes were prepared for breeding experiment: male and female heterozygotes carrying the paternally (+/-p) and maternally (-m/+) transmitted targeted allele. These 4 heterozygotes were bred with their littermates: for Breeding 1, female wild-type littermates x male heterozygotes (+/-P); Breeding 2, female heterozygotes (+/-P) x male wild-type littermates; Breeding 3, female wild-type littermates x male heterozygotes (-m/+); for Breeding 4, female heterozygotes (-m/+) x male wild-type littermates. Genome-wide expression analysis A litter of 14.5-dpc fetuses were harvested from a timed mating between a male heterozygote (-m/+) and wild-type female littermate. Three tissues were obtained from each fetus: embryo head, placenta and amnionic sac. Total 16 samples were used for this series of genome-wide expression analyses: 8 embryo heads and placenta representing two biological replicates of each of the four following combinations: male wild-type, male heterozygote, female wild-type, and female heterozygote.