Besides their clear anatomic phenotype, the SCZ hGPC-chimeric mice manifested robust behavioral phenotypes. They exhibited significantly attenuated prepulse inhibition relative to control-engrafted mice, relative anhedonia, excessive anxiety, deficient socialization with avoidance of conspecifics, and disrupted patterns of diurnal activity and sleep. These data establish that SCZ glial engraftment may yield an abnormal behavioral phenotype in recipient mice, along behavioral axes that typify selected aspects of schizophrenic behavioral pathology in humans. In that regard, while an extensive literature has implicated GPCs (Bergles et al., 2010; De Biase et al., 2010) as well as astroglia (Araque et al., 1998; Kang et al., 1998) in the modulation of synaptic plasticity and learning (Han et al., 2013), our data do not implicate one phenotype over the other in the modulation of behavior by SCZ glial chimerization; our chimeric mice are colonized by both donor-derived human GPCs and their derived astrocytes. That said, our observations of significant defects in SCZ glial maturation shared by hGPCs derived from multiple independent patients, associated in each with hypomyelination and disrupted astrocytic differentiation, as well as with abnormal behavioral
