Figure 2

Whole brain images and cerebellum histology. (a) WT and heterozygous R1098Q mice brains are indistinguishable at birth. By P7, subtle gross and histologic abnormalities begin to emerge in the brains of the R1098Q heterozygotes. These include nearly imperceptible defects in their cerebellar folia and cerebral convolutions. However, at P7 Purkinje cells are abundant and their morphology is intact, excluding developmental failure due to the heterozygous mutation. This is most apparent when immunostained for βIII spectrin that highlights the PC soma and dendrites (insert, shown at 4 × magnification of the H&E stained section; also see supplemental Fig. S3 for enlarged image of the P7 cerebellum). (b) Older R1098Q heterozygote mice (1.5 years) exhibit profound atrophy of the cerebellum, correlating with near total collapse of the molecular layer and loss of Purkinje cells. Some cortical loss can also be perceived. These gradual morphologic changes correlate with the onset of the progressive ataxia apparent in the R1098Q mice, a phenotype that intensifies with age.