Alexis Cooper, Tamer Butto, Niklas Hammer, Somanath Jagannath, Desiree Lucia Fend-Guella, Junaid Akhtar, Konstantin Radyushkin, Florian Lesage, Jennifer Winter, Susanne Strand, Jochen Roeper, Ulrich Zechner, Susann Schweiger
Nature communications 2020 Jan 24Mutations 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.
Alexis Cooper, Tamer Butto, Niklas Hammer, Somanath Jagannath, Desiree Lucia Fend-Guella, Junaid Akhtar, Konstantin Radyushkin, Florian Lesage, Jennifer Winter, Susanne Strand, Jochen Roeper, Ulrich Zechner, Susann Schweiger. Inhibition of histone deacetylation rescues phenotype in a mouse model of Birk-Barel intellectual disability syndrome. Nature communications. 2020 Jan 24;11(1):480
PMID: 31980599
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