of candidate GPCs - the shiverer mouse. Shiverer (MBP shi/shi) is a congenitally hypomyelinated mouse deficient in myelin basic protein (Popko et al. 1987; Readhead et al. 1987). Using immunodeficient shiverer mice as hosts (rag2−/− x MBP shi/shi) (Windrem et al. 2004), we developed a multi-site delivery procedure by which donor GPCs could be introduced into the major presumptive white matter tracts of newborn mice, allowing the broad dispersal of human donor cells throughout the recipient CNS (Windrem et al. 2008). This approach resulted in widespread donor cell engraftment throughout the brain and spinal cord, with infiltration of the forebrain, brainstem and cerebellum, and ultimately the spinal cord and roots (Figure 1). The donor hGPCs exhibited highly efficient oligodendrocyte differentiation and functional myelination in these hypomyelinated mice, with the dense and efficient myelination of congenitally unmyelinated white matter tracts throughout the CNS. This in turn was associated with the substantially prolonged survival of these mice, with frank rescue and phenotypic recovery of a large minority(Windrem et al. 2008). Indeed, whereas untreated shiverers invariably die by 20–21 weeks of age, a fraction of neonatally-engrafted mice achieved normal lifespans of over 2 years, suggesting the potential power of this approach towards remyelinating
