These results may suggest that the Peg3 gene polymorphism found in LG/J dams negatively impacts Peg3 hypothalamic expression. Lower levels of Peg3 transcripts in LG/J females and the heterozygote genotype for the LG/J allele in F2 females were similarly correlated with poor maternal care. Peg3, as the name

implies, is a paternally expressed gene and shows a functional nonequivalence for allelic expression based on parent-of-origin. Imprinted genes have been associated with fetal growth, placental function, and behaviors. Although maternal expression is associated with fetal growth (Tycko and Morison 2002), paternal expression often favors Inhibitors,research,lifescience,medical placental development (Reik et al. 2003), and both modulate neurodevelopment, even in postnatal life (Sirolimus purchase Davies et

al. 2005; Gregg et al. 2010a, b). Recent studies in mice have revealed the increased complexity behind the putative roles for imprinted genes in the brain by showing their spatial and temporal regulation (Gregg Inhibitors,research,lifescience,medical et al. 2010a, b). Although parental effects in the developing and adult brain differ, studies have found that in the adult hypothalamus, approximately 70% of imprinted autosomal genes are preferentially expressed through the paternal allele. Accordingly, Peg3, similar to several other paternally expressed genes in the hypothalamus, is associated with maternal care (Lefebvre et al. 1998; Li et al. 1999; Curley et Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical al. 2004; Champagne et al. 2009), thereby demonstrating the role of epigenetics in mammalian behavior. It is noteworthy that the underdominance for Peg3 in F2 females is an atypical effect for a parent-of-origin gene.

Although the heterozygote effect is not in accordance with what would be expected given the imprinted, paternal expression of Peg3, this dominance pattern was also previously observed in the ovine callipyge gene (Cockett et al. 1996). Mutant, postpartum Peg3 females show reduced immunoreactivity for oxytocin in the hypothalamus when compared with wild-type females, which could explain their impairments in lactation Inhibitors,research,lifescience,medical (Li et al. 1999). In the present study, although hypothalamic Oxt transcript levels were not reduced in LG/J females when compared with those of SM/J mothers, we cannot exclude the possibility of a posttranscriptional effect in this peptide hormone, an effect possibly induced by reduced levels of almost Peg3. In summary, the Peg3 gene maps to the chromosomal region where we previously identified a QTL affecting maternal performance in an intercross of LG/J × SM/J inbred mice. Analysis of the Peg3 gene sequence in LG/J and SM/J female mice revealed several variations leading to amino acid substitutions, as well as a large insertion (10 aa) in a coding region, resulting in a different number of tandem repeats between the strains. Furthermore, Peg3 gene expression in the hypothalamus of LG/J postpartum females is remarkably lower than in SM/J dams.