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 development1, but also postnatal 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 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 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, 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.
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Acknowledgements
We thank S. Wonnacott for reagents, the University of Bath Biological Services Unit and S. Routley for technical assistance, I. Jones and P. Mitchell for advice and C. Tickle for comments on the manuscript. We acknowledge funding of the work from the Biotechnology and Biological Sciences Research Council, Medical Research Council, Wellcome Trust and external benefactors.
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A.W. and A.S.G. conceived the project and interpreted the data, with input from L.D.H., A.R.I. and L.S.W.; K.M. and J.E.S.-C. generated the Grb10KO mice; A.S.G. performed most of the experiments with contributions from M.C., J.W.D., S.B., K.G., A.R.I., F.M.S., J.X. and A.W.; A.S.G. and A.W. jointly wrote the manuscript.
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Garfield, A., Cowley, M., Smith, F. et al. Distinct physiological and behavioural functions for parental alleles of imprinted Grb10. Nature 469, 534–538 (2011). https://doi.org/10.1038/nature09651
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DOI: https://doi.org/10.1038/nature09651
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