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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 unequ...

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Autores principales: Garfield, Alastair S., Cowley, Michael, Smith, Florentia M., Moorwood, Kim, Stewart-Cox, Joanne E., Gilroy, Kerry, Baker, Sian, Xia, Jing, Dalley, Jeffrey W., Hurst, Laurence D., Wilkinson, Lawrence S., Isles, Anthony R., Ward, Andrew
Formato: Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031026/
https://www.ncbi.nlm.nih.gov/pubmed/21270893
http://dx.doi.org/10.1038/nature09651
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author Garfield, Alastair S.
Cowley, Michael
Smith, Florentia M.
Moorwood, Kim
Stewart-Cox, Joanne E.
Gilroy, Kerry
Baker, Sian
Xia, Jing
Dalley, Jeffrey W.
Hurst, Laurence D.
Wilkinson, Lawrence S.
Isles, Anthony R.
Ward, Andrew
author_facet Garfield, Alastair S.
Cowley, Michael
Smith, Florentia M.
Moorwood, Kim
Stewart-Cox, Joanne E.
Gilroy, Kerry
Baker, Sian
Xia, Jing
Dalley, Jeffrey W.
Hurst, Laurence D.
Wilkinson, Lawrence S.
Isles, Anthony R.
Ward, Andrew
author_sort Garfield, Alastair S.
collection PubMed
description 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.
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spelling pubmed-30310262011-07-27 Distinct physiological and behavioural functions for parental alleles of imprinted Grb10 Garfield, Alastair S. Cowley, Michael Smith, Florentia M. Moorwood, Kim Stewart-Cox, Joanne E. Gilroy, Kerry Baker, Sian Xia, Jing Dalley, Jeffrey W. Hurst, Laurence D. Wilkinson, Lawrence S. Isles, Anthony R. Ward, Andrew Nature Article 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. 2011-01-27 /pmc/articles/PMC3031026/ /pubmed/21270893 http://dx.doi.org/10.1038/nature09651 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Garfield, Alastair S.
Cowley, Michael
Smith, Florentia M.
Moorwood, Kim
Stewart-Cox, Joanne E.
Gilroy, Kerry
Baker, Sian
Xia, Jing
Dalley, Jeffrey W.
Hurst, Laurence D.
Wilkinson, Lawrence S.
Isles, Anthony R.
Ward, Andrew
Distinct physiological and behavioural functions for parental alleles of imprinted Grb10
title Distinct physiological and behavioural functions for parental alleles of imprinted Grb10
title_full Distinct physiological and behavioural functions for parental alleles of imprinted Grb10
title_fullStr Distinct physiological and behavioural functions for parental alleles of imprinted Grb10
title_full_unstemmed Distinct physiological and behavioural functions for parental alleles of imprinted Grb10
title_short Distinct physiological and behavioural functions for parental alleles of imprinted Grb10
title_sort distinct physiological and behavioural functions for parental alleles of imprinted grb10
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031026/
https://www.ncbi.nlm.nih.gov/pubmed/21270893
http://dx.doi.org/10.1038/nature09651
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