In this mouse line, white matter astrocytes are also affected, displaying a cytoplasmic pattern of S100β staining that suggests stress.34 The density of immature astrocytes is increased, a characteristic previously described in VWM patients11 and WBM-2b5ho mice.16 Interestingly, the expression of the ATF4 transcriptome is completely normal in the brains of Cnp-2b5ho animals. Here, S100B is linked to leukoencephalopathy with vanishing white matter.