AUTHOR=Su Yan , Liu Junhua , Yu Baocong , Ba Ru , Zhao Chunjie 

TITLE=Brpf1 Haploinsufficiency Impairs Dendritic Arborization and Spine Formation, Leading to Cognitive Deficits

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00249

DOI=10.3389/fncel.2019.00249

ISSN=1662-5102

ABSTRACT=<p>Haploinsufficiency of the bromodomain and PHD finger-containing protein 1 (<italic>BRPF1</italic>) gene causes intellectual disability (ID), which is characterized by impaired intellectual and cognitive function; however, the neurological basis for ID and the neurological function of <italic>BRPF1</italic> dosage in the brain remain unclear. Here, by crossing <italic>Emx1-cre</italic> mice with <italic>Brpf1<sup>fl/fl</sup></italic> mice, we generated <italic>Brpf1</italic> heterozygous mice to model <italic>BRPF1</italic>-related ID. <italic>Brpf1</italic> heterozygotes showed reduced dendritic complexity in both hippocampal granule cells and cortical pyramidal neurons, accompanied by reduced spine density and altered spine and synapse morphology. An <italic>in vitro</italic> study of <italic>Brpf1</italic> haploinsufficiency also demonstrated decreased frequency and amplitude of miniature EPSCs that may subsequently contribute to abnormal behaviors, including decreased anxiety levels and defective learning and memory. Our results demonstrate a critical role for <italic>Brpf1</italic> dosage in neuron dendrite arborization, spine morphogenesis and behavior and provide insight into the pathogenesis of <italic>BRPF1</italic>-related ID.</p>