Distinct physiological and behavioural functions for parental alleles of imprinted Grb10

Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development1, but also post-natal functions including energy homeostasis2 and behaviour3, 4. When the two parental alleles are unequally represented within a social group (when there is sex-bias in dispersal and/or variance in reproductive success)5, 6, imprinted genes may evolve to modulate social behaviour, although to date no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adapter protein that can interact with a number of receptor tyrosine kinases and downstream signalling molecules7. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10 deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus, Grb10 is to date a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, due to actions of the two parental alleles in different tissues.