A Novel Mutant Allele of Pw1/Peg3 Does Not Affect Maternal Behavior or Nursing Behavior

Parental imprinting is a mammalian-specific form of epigenetic regulation in which one allele of a gene is silenced depending on its parental origin. Parentally imprinted genes have been shown to play a role in growth, metabolism, cancer, and behavior. Although the molecular mechanisms underlying parental imprinting have been largely elucidated, the selective advantage of silencing one allele remains unclear. The mutant phenotype of the imprinted gene, Pw1/Peg3, provides a key example to illustrate the hypothesis on a coadaptation between mother and offspring, in which Pw1/Peg3 is required for a set of essential maternal behaviors, such as nursing, nest building, and postnatal care. We have generated a novel Pw1/Peg3 mutant allele that targets the last exon for the PW1 protein that contains >90% of the coding sequence resulting in a loss of Pw1/Peg3 expression. In contrast to previous reports that have targeted upstream exons, we observe that maternal behavior and lactation are not disrupted upon loss of Pw1/Peg3. Both paternal and homozygous Pw1/Peg3 mutant females nurse and feed their pups properly and no differences are detected in either oxytocin neuron number or oxytocin plasma levels. In addition, suckling capacities are normal in mutant pups. Consistent with previous reports, we observe a reduction of postnatal growth. These results support a general role for Pw1/Peg3 in the regulation of body growth but not maternal care and lactation.Author Summary: Parental genomic imprinting is a mammalian-specific form of epigenetic control that regulates genes differently depending upon whether they are paternally or maternally inherited. The selective advantage of genomic imprinting is poorly understood and has been the subject of numerous theories. In the last several decades, mouse genetic studies have revealed that imprinted genes regulate embryonic and postnatal growth, metabolism, stem cells, neuronal functions, and most notably, behavior. The paternally expressed gene Pw1/Peg3 was one of the first imprinted genes shown to influence maternal behaviors essential for pup survival and growth. Several key studies have demonstrated that Pw1/Peg3 is required for proper nursing and milk ejection by the mother and suckling by the offspring. These previous observations have provided a strong support for the coadaptation theory of imprinting, which proposes that imprinted genes regulate the use of resources between mother and progeny to optimize their survival and future reproductive success. Here we describe that Pw1/Peg3 mutant females exhibit intact maternal behaviors and do not display milk ejection defects. In addition, mutant pups are able to nurse properly.