Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour
IntroductionImprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their parent-of-origin. Recent research suggests that the sex of the individual expressing the imprinte...
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2024.1374781/full |
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| author | Hannah R. Tyson David J. Harrison Mathew J. Higgs Anthony R. Isles Rosalind M. John |
| author_facet | Hannah R. Tyson David J. Harrison Mathew J. Higgs Anthony R. Isles Rosalind M. John |
| author_sort | Hannah R. Tyson |
| collection | DOAJ |
| description | IntroductionImprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their parent-of-origin. Recent research suggests that the sex of the individual expressing the imprinted gene is also important. We have previously reported that genetically wildtype (WT) dams carrying and caring for pups mutant for PEG3 exhibit anxiety-like behaviours and their mutant pups show a reduction in ultrasonic vocalisation when separated from their mothers. Sex-specificity was not examined.MethodsWT female mice were mated with WT, heterozygous Peg3−/+ or homozygous Peg3−/− studs to generate all WT (control), 50:50 mixed or 100% mutant litters, respectively, followed by behavioural assessment of both dams and their pups.ResultsWe reproduced our original finding that WT dams carrying and caring for 100% mutant litters exhibit postpartum anxiety-like symptoms and delayed pup retrieval. Additionally, these WT dams were found to allocate less time to pup-directed care behaviours relative to controls. Male Peg3-deficient pups demonstrated significantly reduced vocalisation with a more subtle communication deficit in females. Postweaning, male mutants exhibited deficits across a number of key social behaviours as did WT males sharing their environment with mutants. Only modest variations in social behaviour were detected in experimental females.DiscussionWe have experimentally demonstrated that Peg3 deficiency confined to the offspring causes anxiety in mouse mothers and atypical behaviour including deficits in communication in their male offspring. A male-specific reduction in expression PEG3 in the fetally-derived placenta has previously been associated with maternal depression in human pregnancy. Maternal mood disorders such as depression and anxiety are associated with delays in language development and neuroatypical behaviour more common in sons. Peg3 deficiency could drive the association of maternal and offspring behavioural disorders reported in humans. |
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| language | English |
| last_indexed | 2024-04-24T19:17:46Z |
| publishDate | 2024-03-01 |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-bd56a482532e491f80afd8b6b5191d782024-03-26T04:57:47ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2024-03-011810.3389/fnins.2024.13747811374781Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviourHannah R. Tyson0David J. Harrison1Mathew J. Higgs2Anthony R. Isles3Rosalind M. John4Biomedicine Division, School of Biosciences, Cardiff University, Cardiff, United KingdomBiomedicine Division, School of Biosciences, Cardiff University, Cardiff, United KingdomBehavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United KingdomBehavioural Genetics Group, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United KingdomBiomedicine Division, School of Biosciences, Cardiff University, Cardiff, United KingdomIntroductionImprinted genes are expressed from one parental allele as a consequence of epigenetic processes initiated in the germline. Consequently, their ability to influence phenotype depends on their parent-of-origin. Recent research suggests that the sex of the individual expressing the imprinted gene is also important. We have previously reported that genetically wildtype (WT) dams carrying and caring for pups mutant for PEG3 exhibit anxiety-like behaviours and their mutant pups show a reduction in ultrasonic vocalisation when separated from their mothers. Sex-specificity was not examined.MethodsWT female mice were mated with WT, heterozygous Peg3−/+ or homozygous Peg3−/− studs to generate all WT (control), 50:50 mixed or 100% mutant litters, respectively, followed by behavioural assessment of both dams and their pups.ResultsWe reproduced our original finding that WT dams carrying and caring for 100% mutant litters exhibit postpartum anxiety-like symptoms and delayed pup retrieval. Additionally, these WT dams were found to allocate less time to pup-directed care behaviours relative to controls. Male Peg3-deficient pups demonstrated significantly reduced vocalisation with a more subtle communication deficit in females. Postweaning, male mutants exhibited deficits across a number of key social behaviours as did WT males sharing their environment with mutants. Only modest variations in social behaviour were detected in experimental females.DiscussionWe have experimentally demonstrated that Peg3 deficiency confined to the offspring causes anxiety in mouse mothers and atypical behaviour including deficits in communication in their male offspring. A male-specific reduction in expression PEG3 in the fetally-derived placenta has previously been associated with maternal depression in human pregnancy. Maternal mood disorders such as depression and anxiety are associated with delays in language development and neuroatypical behaviour more common in sons. Peg3 deficiency could drive the association of maternal and offspring behavioural disorders reported in humans.https://www.frontiersin.org/articles/10.3389/fnins.2024.1374781/fullepigeneticsimprinted genesPeg3sexual dimorphismultrasonic vocalisationsocial behaviour |
| spellingShingle | Hannah R. Tyson David J. Harrison Mathew J. Higgs Anthony R. Isles Rosalind M. John Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour Frontiers in Neuroscience epigenetics imprinted genes Peg3 sexual dimorphism ultrasonic vocalisation social behaviour |
| title | Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour |
| title_full | Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour |
| title_fullStr | Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour |
| title_full_unstemmed | Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour |
| title_short | Deficiency of the paternally-expressed imprinted Peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour |
| title_sort | deficiency of the paternally expressed imprinted peg3 gene in mice has sexually dimorphic consequences for offspring communication and social behaviour |
| topic | epigenetics imprinted genes Peg3 sexual dimorphism ultrasonic vocalisation social behaviour |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2024.1374781/full |
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