βPix heterozygous mice have defects in neuronal morphology and social interaction

Abstract

βPix activates Rho family small GTPases, Rac1 and Cdc42 as a guanine nucleotide exchange factor. Although overexpression of βPix in cultured neurons indicates that βPix is involved in spine morphogenesis and synapse formation in vitro, the in vivo role of βPix in the neuron is not well understood. Recently, we generated βPix knockout mice that showed lethality at embryonic day 9.5. Here, we investigate the neuronal role of βPix using βPix heterozygous mice that are viable and fertile. βPix heterozygous mice show decreased expression levels of βPix proteins in various tissues including the brain. Cultured hippocampal neurons from βPix heterozygous mice show a decrease in neurite length and complexity as well as synaptic density. Both excitatory and inhibitory synapse densities are decreased in these neurons. Golgi-staining of hippocampal tissues from the brain of these mice show reduced dendritic complexity and spine density in the hippocampal neurons. Expression levels of NMDA- and AMPA-receptor subunits and Git1 protein in hippocampal tissues are also decreased in these mice. Behaviorally, βPix heterozygous mice exhibit impaired social interaction. Altogether, these results indicate that βPix is required for neurite morphogenesis and synapse formation, and the reduced expression of βPix proteins results in a defect in social behavior.