In this study, we created human glial-chimeric mice, in which immunodeficient but otherwise normal mice were engrafted neonatally with large numbers of human glial progenitors, resulting in the widespread integration of human glia into the mouse brain. By the time these mice reached adulthood, a large proportion of their forebrain glia were replaced by human cells. The chimerization was slowly progressive, so that extensive infiltration of cortex and hippocampus by human cells was evident by 4-12 months (Fig. 1). The xenografted human cells remained as NG2-defined glial progenitor cells or differentiated as hGFAP+ astrocytes; remarkably, the latter maintained their characteristic, large and complex hominid-selective morphologies (Fig. 2). In addition, some assumed the characteristic long-distance fiber extensions of interlaminar astrocytes, a domain-traversing astrocytic phenotype specific to the hominid brain (Colombo, 2001; Colombo et al., 1995; Oberheim et al., 2006). Electrophysiological analysis validated that most EGFP+/hGFAP+/hNuclei+ human glia were protoplasmic astrocytes, based on their low input resistance, passive membrane properties, extensive gap junction coupling, and Ca2+ wave propagation (Fig. 3).
