Figure 4.

Differential genetic interaction with Apoer2^null and Vldlr^null mice in the cerebellum. A, Gross morphology of the cerebellum. B–D, Immunohistochemistry images of P21 brain sagittal sections at the level of the vermis are shown. Anti-calbindin (red, Purkinje cells) and anti-NeuN (green, granule cells) antibodies were used. B, Reln^CTRdel/Apoer2^null double-homozygote mice display a smaller and less foliated cerebellum than either mutant alone. Reln^CTRdel/Vldlr^null double-homozygote display a foliation pattern similar to that of Vldlr^null mice. Ten cerebellar lobules (I–X) are labeled. Scale bar, 500 μm. C, High-magnification images of the cerebellar white matter (WM) region taken from the same section shown in B. Reln^CTRdel/Apoer2^null double homozygote mice, as well as Apoer2^null mice, have ectopically localized calbindin-expressing Purkinje cells (red) at the level of the vermis. Scale bar, 250 μm. D, High-magnification images of the cerebellar granule cell layer (GCL) taken from the same section shown in B. Disorganized layers of the granule cells and Purkinje cells (PCL) seen in Vldlr^null mice are less severe in Reln^CTRdel/Vldlr^null mice. ML, molecular layer. Scale bar, 200 μm.