The role of ARID1B, a BAF chromatin remodeling complex subunit, in neural development and behavior

Progress in Neuro-psychopharmacology & Biological Psychiatry
Jeffrey Jay MoffatWoo-Yang Kim

Abstract

Haploinsufficiency of the chromatin remodeling factor ARID1B leads to autism spectrum disorder and intellectual disability. Several independent research groups, including our own, recently examined the effects of heterozygous deletion of Arid1b in mice and reported severe behavioral abnormalities reminiscent of autism spectrum disorders and intellectual disability as well as marked changes in gene expression and decreased body size. Arid1b heterozygous mice also display significant cortical excitatory/inhibitory imbalance due to altered GABAergic neuron numbers and impaired inhibitory synaptic transmission. Abnormal epigenetic modifications, including histone acetylation and methylation, are additionally associated with Arid1b haploinsufficiency in the brain. Treating adult Arid1b mutant mice with a positive GABA allosteric modulator, however, rescues multiple behavioral abnormalities, such as cognitive and social impairments, as well as elevated anxiety. While treating Arid1b haploinsufficient mice with recombinant mouse growth hormone successfully increases body size, it has no effect on aberrant behavior. Here we summarize the recent findings regarding the role of ARID1B in brain development and behavior and discuss the util...Continue Reading

Citations

Mar 23, 2021·Frontiers in Cell and Developmental Biology·Luca Pagliaroli, Marco Trizzino
Sep 10, 2020·Current Opinion in Neurobiology·Iva B Zovkic
Jul 10, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jessica J WalshRobert C Malenka

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