A Drosophila Model of Intellectual Disability Caused by Mutations in the Histone Demethylase KDM5.

ABSTRACT: Mutations in KDM5 family histone demethylases cause intellectual disability in humans. However, the molecular mechanisms linking KDM5-regulated transcription and cognition remain unknown. Here, we establish Drosophila as a model to understand this connection by generating a fly strain harboring an allele analogous to a disease-causing missense mutation in human KDM5C (kdm5^A512P). Transcriptome analysis of kdm5^A512P flies revealed a striking downregulation of genes required for ribosomal assembly and function and a concomitant reduction in translation. kdm5^A512P flies also showed impaired learning and/or memory. Significantly, the behavioral and transcriptional changes in kdm5^A512P flies were similar to those specifically lacking demethylase activ

SUBMITTER: Zamurrad S 

PROVIDER: S-EPMC5854480 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature