Effects of noncanonical genomic imprinting in monoaminergic pathways on the regulation of social behaviors

Abstract

AbstractGenomic imprinting in the brain is theorized to provide parental control over offspring social behaviors. Noncanonical genomic imprinting is a form of epigenetic regulation in which one of a gene’s alleles, either that of maternal or paternal inheritance, exhibits a bias towards higher expression of one parental allele compared to the other. This bias can differ depending on tissue type, and the degree of the parental allele expression bias can even vary across anatomical domains within the same tissue. Dopa decarboxylase (Ddc) and tyrosine hydroxylase (Th) are both noncanonically imprinted genes that preferentially express their maternal alleles in the brain andDdcalso has a paternal allele expression bias in the periphery. These two genes encode catecholamine synthesis enzymes for the production of dopamine (DA), norepinephrine (NE), and epinephrine (E), andDdcis also in the serotonin (5-HT) synthesis pathway. These four neurotransmitters are critical regulators of social behavior and disruptions to them are implicated in human mental illnesses. Here we investigated the functional effects of noncanonical imprinting ofDdcandThon social behavior in mice. By using reciprocal heterozygous mutant mice, we tested the impacts ofDdcand/orThmaternally and paternally inherited alleles on aggression, social recognition, dominance, and social preference behaviors. We found thatDdcpaternal-null alleles affect aggression and social recognition behavior,Thmaternal-null alleles affect sociability preferences, and compound inheritance ofThandDdcmaternal-null alleles influence preferences for social novelty. These results are consistent withThandDdcmaternal allele biased expression in central monoaminergic systems regulating sociability, andDdcpaternal allele biased expression in peripheral monoaminergic systems regulating aggression and social recognition.