Distinct physiological and behavioural functions for parental alleles of imprinted Grb10

A S Garfield, Michael Cowley, F M Smith, Kim Moorwood, Joanne E Stewart-Cox, K Gilroy, S Baker, J Xia, J W Dalley, Laurence D Hurst, L S Wilkinson, A R Isles, Andrew Ward

Research output: Contribution to journalArticle

117 Citations (Scopus)

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(1), but also postnatal functions including energy homeostasis(2) and behaviour(3,4). 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 molecules(7). 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.
Original languageEnglish
Pages (from-to)534-538
Number of pages5
JournalNature
Volume469
Issue number7331
DOIs
Publication statusPublished - 27 Jan 2011

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alleles
social behavior
embryogenesis
genes
social dominance
fetal development
adulthood
tyrosine
homeostasis
phosphotransferases (kinases)
brain
receptors
genome
gender
energy
animals
proteins
tissues

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Distinct physiological and behavioural functions for parental alleles of imprinted Grb10. / Garfield, A S; Cowley, Michael; Smith, F M; Moorwood, Kim; Stewart-Cox, Joanne E; Gilroy, K; Baker, S; Xia, J; Dalley, J W; Hurst, Laurence D; Wilkinson, L S; Isles, A R; Ward, Andrew.

In: Nature, Vol. 469, No. 7331, 27.01.2011, p. 534-538.

Research output: Contribution to journalArticle

Garfield, AS, Cowley, M, Smith, FM, Moorwood, K, Stewart-Cox, JE, Gilroy, K, Baker, S, Xia, J, Dalley, JW, Hurst, LD, Wilkinson, LS, Isles, AR & Ward, A 2011, 'Distinct physiological and behavioural functions for parental alleles of imprinted Grb10', Nature, vol. 469, no. 7331, pp. 534-538. https://doi.org/10.1038/nature09651
Garfield, A S ; Cowley, Michael ; Smith, F M ; Moorwood, Kim ; Stewart-Cox, Joanne E ; Gilroy, K ; Baker, S ; Xia, J ; Dalley, J W ; Hurst, Laurence D ; Wilkinson, L S ; Isles, A R ; Ward, Andrew. / Distinct physiological and behavioural functions for parental alleles of imprinted Grb10. In: Nature. 2011 ; Vol. 469, No. 7331. pp. 534-538.
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