RO4938581, a GABA_A-α5 negative allosteric modulator rescued behavioral and EEG phenotypes of a mouse model of Dup15q syndrome.

ABSTRACT: We investigated the correlation between increased gene copy number of gamma aminobutyric acid type A (GABA_A) receptor α5-containing subunits and electrophysiological and behavioral phenotypes in a mouse model of Dup15q syndrome (15q dup) and tested the hypothesis that selectively inhibiting the activity of GABA_A-α5 receptors may have therapeutic effects. Dup15q syndrome is a rare neurodevelopmental disorder caused by copy number gains of the 15q11.2-q13.1 chromosomal region, which includes UBE3A and a cluster of three genes (GABRA5, GABRB3, and GABRG3) encoding GABA_A receptor subunits, all of which are critical for neural development and function. Most affected children display hypotonia, motor delays, intellectual disability, and epilepsy, as well as a cha

SUBMITTER: Nakagawa R 

PROVIDER: S-EPMC12916284 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature