Project description: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.
Project description: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. 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.
