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

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 (Kcnk9 pat) 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.
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https://www.hal.inserm.fr/inserm-02495599
Contributor : Myriam Bodescot <>
Submitted on : Monday, March 2, 2020 - 12:38:15 PM
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Alexis Cooper, Tamer Butto, Niklas Hammer, Somanath Jagannath, Desiree Fend-Guella, et al.. Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.480. ⟨10.1038/s41467-019-13918-4⟩. ⟨inserm-02495599⟩

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