Since the SCZ hGPC-engrafted shiverers manifested deficient myelination, we asked whether this was due to a relative failure of SCZ hGPCs to remain within white matter, or rather to a cell-intrinsic failure in myelinogenesis. Examining 19 wk-old SCZ and control hGPC-engrafted shiverer mice, we found significantly fewer human nuclear antigen (hNA)-defined donor-derived cells in SCZ hGPC-engrafted shiverer white matter (40,615 ± 2,189 × 103 hNA+ cells/mm3, n=18) than in mice identically transplanted with control hGPCs (69,970 ± 4,091/mm3; n=32; p<0.0001 by 2-tailed t test (Fagerland and Sandvik, 2009; Zimmerman, 2004)) (Figure 2H). Moreover, the numbers of hNA+ donor cells co-expressing the oligodendroglial lineage marker Olig2 were similarly depressed in the SCZ hGPC-engrafted mice (33,619 ± 2,435/mm3, n=26), relative to control hGPC-engrafted mice (46,139 ± 2,858/mm3, n=17; p<0.002) (Figure 2I). On that basis, we next found that the density of transferrin-defined human oligodendroglia was similarly lower in the callosal white matter of SCZ hGPC chimeras, than in control hGPC chimeras (8,778±892.2/mm3, n=25; vs. 17,754±2,023/mm3, n=17, respectively; p=0.0006, Mann-Whitney) (Figure 2J). These data indicate that SCZ GPCs are deficient not only in
