Peg13 regulates sexual preference

Mammalian genomes include many maternally or paternally imprinted genes. Most of these are also expressed in the brain and several were previously implicated in regulating specific behavioral traits. We have used here a knockout approach to study the function of Peg13. Peg13 codes for a fast evolving lncRNA and is part of a complex of imprinted genes on chromosome 15 in the mouse and chromosome 8 in humans. Two knockout constructs were analyzed, one with a full deletion of the gene, the other with a deletion of the 3 ´-half. The full deletion is semi lethal, while the partial deletion is fully viable, but the mice show distinctive behavioral differences. They lose interest in the opposite sex and show instead a preference for wildtype animals of the same sex. Further, they show a higher level of anxiety, as well as lowered activity and curiosity and females have a deficiency in pup retrieval behavior. Brain RNA expression analysis reveals that genes involved in the serotonergic system, formation of glutamergic synapses, olfactory processing and estrogen signaling, as well as more than half of the other known imprinted genes are affected in Peg13 deficient mice. Intriguingly, the pathways are differentially affected in the sexes, with the result that the male and female brains of Peg13 deficient mice differ more from each other than those of wildtype mice. We conclude that Peg13 is part of a developmental pathway that regulates the neurobiology of social interactions.