Behavioural effects of imprinted genes

Davies, Jennifer R.; Dent, Claire L.; McNamara, Gráinne; Isles, Anthony R

doi:10.1016/j.cobeha.2014.07.008

Cited by 12 publications

(11 citation statements)

References 47 publications

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“…Our data provide a novel mode of action for genomic imprinting in the brain, adding to the list of behaviours sensitive to imprinted gene function (Davies et al 2015). Imprinted genes are thought to have evolved as a consequence of conflicting phenotypic 'interests' between maternal and paternal genes, which causes an escalating arms race in relation to allelic expression, eventually leading to silencing of one or other parental allele (Moore and Haig 1991;Wilkins and Haig 2003).…”

Section: Discussionmentioning

confidence: 93%

Impulsive choices in mice lacking imprinted Nesp55

Dent

Humby

Lewis

et al. 2016

Genes Brain and Behavior

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Genomic imprinting is the process whereby germline epigenetic events lead to parent-of-origin specific monallelic expression of a number of key mammalian genes. The imprinted gene Nesp is expressed from the maternal allele only and encodes for Nesp55 protein. In the brain, Nesp55 is found predominately in discrete areas of the hypothalamus and midbrain. Previously, we have shown that loss of Nesp55 gives rise to alterations in novelty-related behaviour. Here, we extend these findings and demonstrate, using the Nesp mouse model, that loss of Nesp55 leads to impulsive choices as measured by a delayed-reinforcement task, whereby Nesp mice were less willing to wait for a delayed, larger reward, preferring instead to choose an immediate, smaller reward. These effects were highly specific as performance in another component of impulsive behaviour, the ability to stop a response once started as assayed in the stop-signal reaction time task, was equivalent to controls. We also showed changes in the serotonin system, a key neurotransmitter pathway mediating impulsive behaviour. First, we demonstrated that Nesp55 is co-localized with serotonin and then went on to show that in midbrain regions there were reductions in mRNA expression of the serotonin-specific genes Tph2 and Slc6a4, but not the dopamine-specific gene Th in Nesp mice; suggesting an altered serotonergic system could contribute, in part, to the changes in impulsive behaviour. These data provide a novel mode of action for genomic imprinting in the brain and may have implications for pathological conditions characterized by maladaptive response control.

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Section: Discussionmentioning

confidence: 93%

Impulsive choices in mice lacking imprinted Nesp55

Dent

Humby

Lewis

et al. 2016

Genes Brain and Behavior

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“…Imprinted genes are also important for brain development and behavior ( Davies et al, 2015 ), with some evolutionary ideas pointing to social behaviors as being particularly targeted ( Brandvain et al, 2011 ; McNamara and Isles, 2014 ). We have previously shown that animals with a loss of neural expression of the imprinted gene Growth factor receptor bound protein 10 ( Grb10 ) displayed altered social behavior.…”

Section: Introductionmentioning

confidence: 99%

Territorial Behavior and Social Stability in the Mouse Require Correct Expression of Imprinted Cdkn1c

McNamara

Roshan

Isles

2018

Front. Behav. Neurosci.

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Genomic imprinting, the epigenetic process by which transcription occurs from a single parental allele, is believed to influence social behaviors in mammals. An important social behavior is group living, which is enriched in Eutherian mammals relative to monotremes and marsupials. Group living facilitates resource acquisition, defense of territory and co-care of young, but requires a stable social group with complex inter-individual relationships. Co-occurring with increased group living in Eutherians is an increase in the number of imprinted loci, including that spanning the maternally expressed Cdkn1c. Using a ‘loss-of-imprinting’ model of Cdkn1c (Cdkn1cBACx1), we demonstrated that twofold over expression of Cdkn1c results in abnormal social behaviors. Although, our previous work indicated that male Cdkn1cBACx1 mice were more dominant as measured by tube test encounters with unfamiliar wild-type (WT) males. Building upon this work, using more ecologically relevant assessments of social dominance, indicated that within their normal social group, Cdkn1cBACx1 mice did not occupy higher ranking positions. Nevertheless, we find that presence of Cdkn1cBACx1 animals within a group leads to instability of the normal social hierarchy, as indicated by greater variability in social rank within the group over time and an increase in territorial behavior in WT cage-mates. Consequently, these abnormal behaviors led to an increased incidence of fighting and wounding within the group. Taken together these data indicate that normal expression of Cdkn1c is required for maintaining stability of the social group and suggests that the acquisition of monoallelic expression of Cdkn1c may have enhanced social behavior in Eutherian mammals to facilitate group living.

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“…) and behaviour (Davies et al . ). Furthermore, imprinted gene function is sensitive to dosage as exemplified by human imprinting disorders that arise from improper imprinted gene expression levels.…”

mentioning

confidence: 97%

“…This class of genes were identified following on from the observation of the non-equivalence of the parental genomes in androgenetic, gynogenetic and parthenogenetic murine embryos resulting in embryonic fatality (McGrath & Solter 1984;Surani et al 1984). The function of these genes converge on key aspects of mammalian physiology including placental development and function (Tunster et al 2013), metabolism (Smith et al 2006) and behaviour (Davies et al 2015). Furthermore, imprinted gene function is sensitive to dosage as exemplified by human imprinting disorders that arise from improper imprinted gene expression levels.…”

mentioning

confidence: 99%

Dopaminergic and behavioural changes in a loss‐of‐imprinting model of Cdkn1c

McNamara

Davis

Browne

et al. 2017

Genes Brain and Behavior

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The imprinted gene Cdkn1c is expressed exclusively from the maternally inherited allele as a consequences of epigenetic regulation. Cdkn1c exemplifies many of the functional characteristics of imprinted genes, playing a role in foetal growth and placental development. However, Cdkn1c also plays an important role in the brain, being key to the appropriate proliferation and differentiation of midbrain dopaminergic neurons. Using a transgenic model (Cdkn1c BACx1) with a twofold elevation in Cdkn1c expression that mimics loss‐of‐imprinting, we show that increased expression of Cdkn1c in the brain gives rise to neurobiological and behavioural changes indicative of a functionally altered dopaminergic system. Cdkn1c BACX1 mice displayed altered expression of dopamine system‐related genes, increased tyrosine hydroxylase (Th) staining and increased tissue content of dopamine in the striatum. In addition, Cdkn1c BACx1 animals were hypersensitive to amphetamine as showed by c‐fos expression in the nucleus accumbens. Cdkn1c BACX1 mice had significant changes in behaviours that are dependent on the mesolimbic dopaminergic system. Specifically, increased motivation for palatable food stuffs, as indexed on a progressive ratio task. In addition, Cdkn1c BACX1 mice displayed enhanced social dominance. These data show, for the first time, the consequence of elevated Cdkn1c expression on dopamine‐related behaviours highlighting the importance of correct dosage of this imprinted gene in the brain. This work has significant relevance for deepening our understanding of the epigenetic factors that can shape neurobiology and behaviour.

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Behavioural effects of imprinted genes

Cited by 12 publications

References 47 publications

Impulsive choices in mice lacking imprinted Nesp55

Impulsive choices in mice lacking imprinted Nesp55

Territorial Behavior and Social Stability in the Mouse Require Correct Expression of Imprinted Cdkn1c

Dopaminergic and behavioural changes in a loss‐of‐imprinting model of Cdkn1c

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