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Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice

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  • Ryan M. Walsh

    (Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital
    Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute
    Howard Hughes Medical Institute)

  • Erica Y. Shen

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Rosemary C. Bagot

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
    Present address: Department of Psychology, McGill University, Montreal, Canada H3A 0G4)

  • Anthony Anselmo

    (Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital)

  • Yan Jiang

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Behnam Javidfar

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Gregory J. Wojtkiewicz

    (Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School)

  • Jennifer Cloutier

    (Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital
    Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute
    Howard Hughes Medical Institute)

  • John W. Chen

    (Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Ruslan Sadreyev

    (Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital)

  • Eric J. Nestler

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Schahram Akbarian

    (Friedman Brain Institute, Icahn School of Medicine at Mount Sinai)

  • Konrad Hochedlinger

    (Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital
    Department of Stem Cell and Regenerative Biology and Harvard Stem Cell Institute
    Howard Hughes Medical Institute)

Abstract

PHF8 is a histone demethylase with specificity for repressive modifications. While mutations of PHF8 have been associated with cognitive defects and cleft lip/palate, its role in mammalian development and physiology remains unexplored. Here, we have generated a Phf8 knockout allele in mice to examine the consequences of Phf8 loss for development and behaviour. Phf8 deficient mice neither display obvious developmental defects nor signs of cognitive impairment. However, we report a striking resiliency to stress-induced anxiety- and depression-like behaviour on loss of Phf8. We further observe misregulation of serotonin signalling within the prefrontal cortex of Phf8 deficient mice and identify the serotonin receptors Htr1a and Htr2a as direct targets of PHF8. Our results clarify the functional role of Phf8 in mammalian development and behaviour and establish a direct link between Phf8 expression and serotonin signalling, identifying this histone demethylase as a potential target for the treatment of anxiety and depression.

Suggested Citation

  • Ryan M. Walsh & Erica Y. Shen & Rosemary C. Bagot & Anthony Anselmo & Yan Jiang & Behnam Javidfar & Gregory J. Wojtkiewicz & Jennifer Cloutier & John W. Chen & Ruslan Sadreyev & Eric J. Nestler & Scha, 2017. "Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice," Nature Communications, Nature, vol. 8(1), pages 1-11, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15142
    DOI: 10.1038/ncomms15142
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    Cited by:

    1. Aleix Arnau-Soler & Mark J Adams & Generation Scotland & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium & Caroline Hayward & Pippa A Thomson, 2018. "Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder," PLOS ONE, Public Library of Science, vol. 13(12), pages 1-29, December.

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