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 (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.

SUBMITTER: Cooper A 

PROVIDER: S-EPMC6981138 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature