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Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome

Author

Listed:
  • Alexis Cooper

    (University Medical Center of the Johannes Gutenberg University Mainz)

  • Tamer Butto

    (Johannes Gutenberg University Mainz)

  • Niklas Hammer

    (Goethe University Frankfurt)

  • Somanath Jagannath

    (Goethe University Frankfurt)

  • Desiree Lucia Fend-Guella

    (University Medical Center of the Johannes Gutenberg University Mainz)

  • Junaid Akhtar

    (Johannes Gutenberg University Mainz)

  • Konstantin Radyushkin

    (University Medical Center of the Johannes Gutenberg University Mainz)

  • Florian Lesage

    (Université Côte d’Azur, INSERM, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Labex ICST)

  • Jennifer Winter

    (University Medical Center of the Johannes Gutenberg University Mainz
    University Medical Center of the Johannes Gutenberg University Mainz)

  • Susanne Strand

    (University Medical Center of the Johannes Gutenberg University Mainz)

  • Jochen Roeper

    (Goethe University Frankfurt)

  • Ulrich Zechner

    (University Medical Center of the Johannes Gutenberg University Mainz
    Senckenberg Center of Human Genetics)

  • Susann Schweiger

    (University Medical Center of the Johannes Gutenberg University Mainz
    University Medical Center of the Johannes Gutenberg University Mainz
    University Medical Center of the Johannes Gutenberg University Mainz
    University Medical Center of the Johannes Gutenberg University Mainz)

Abstract

Mutations in the actively expressed, maternal allele of the imprinted KCNK9 gene cause Birk-Barel intellectual disability syndrome (BBIDS). Using a BBIDS mouse model, we identify here a partial rescue of the BBIDS-like behavioral and neuronal phenotypes mediated via residual expression from the paternal Kcnk9 (Kcnk9pat) allele. We further demonstrate that the second-generation HDAC inhibitor CI-994 induces enhanced expression from the paternally silenced Kcnk9 allele and leads to a full rescue of the behavioral phenotype suggesting CI-994 as a promising molecule for BBIDS therapy. Thus, these findings suggest a potential approach to improve cognitive dysfunction in a mouse model of an imprinting disorder.

Suggested Citation

  • Alexis Cooper & Tamer Butto & Niklas Hammer & Somanath Jagannath & Desiree Lucia Fend-Guella & Junaid Akhtar & Konstantin Radyushkin & Florian Lesage & Jennifer Winter & Susanne Strand & Jochen Roeper, 2020. "Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13918-4
    DOI: 10.1038/s41467-019-13918-4
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