title: Distinct physiological and behavioural functions for parental alleles of imprinted Grb10.
abstract: 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 development, but also postnatal functions including energy homeostasis and behaviour. 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), imprinted genes may evolve to modulate social behaviour, although so far no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adaptor protein that can interact with several receptor tyrosine kinases and downstream signalling molecules. 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, so far, a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, owing to actions of the two parental alleles in different tissues.
authors.affiliation: Department of Biology & Biochemistry and Centre for Regenerative Medicine, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Alastair S
authors.initials: AS
authors.lastname: Garfield
authors.forename: Michael
authors.initials: M
authors.lastname: Cowley
authors.forename: Florentia M
authors.initials: FM
authors.lastname: Smith
authors.forename: Kim
authors.initials: K
authors.lastname: Moorwood
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Stewart-Cox
authors.forename: Kerry
authors.initials: K
authors.lastname: Gilroy
authors.forename: Sian
authors.initials: S
authors.lastname: Baker
authors.forename: Jing
authors.initials: J
authors.lastname: Xia
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Dalley
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Wilkinson
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Isles
authors.forename: Andrew
authors.initials: A
authors.lastname: Ward
mesh_terms: D000483:Alleles; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002490:Central Nervous System / Q000196:embryology; D005260:Female; D051383:GRB10 Adaptor Protein / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D012930:Social Dominance
chemical_list: C495959:Grb10 protein, mouse; D051383:GRB10 Adaptor Protein