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Fig. 6. Adult Nestin-Cre conditional {alpha}v mutants develop axonal degeneration in the spinal cord and cerebellum. (A,B) Cross-sections through the thoracic region of spinal cords from six-month-old control (A) and mutant (B) mice stained to visualize myelin. The axonal tracts of the white matter (wm) stain intensely blue when compared with the grey matter (gm). (C,D) Higher magnification images of grey matter (dashed boxes in A,B) from control (C) or mutant (D) spinal cords. Motoneurons in both controls and mutants are myelinated and show normal cytoarchitecture (arrows in C,D). (E,F) Higher magnification of fasciculus gracilis white matter region in control (E) and mutant (F) spinal cords (solid boxes in A,B). The myelin pattern is disorganized in the mutant, with obvious regions of macrophage infiltration (arrows in F). (G,H) Caudal cerebellar regions from 6-month-old control (G) and mutant (H) mice were stained to visualize myelin. Representative cerebellar folia are shown, with the cerebellar white matter (wm) surrounded by the granule cell layers (gcl) and molecular layers (ml). Overall cerebellum size and patterning in the control (G) and mutant (H) appear normal. (I,J) Higher magnification images from boxed regions in G,H, respectively. The mutant white matter is pale and has an abnormal pattern of myelination (H,J) when compared with the control (G,I). Macrophage infiltration is also obvious in the mutant white matter, with many macrophages containing Luxol Fast Blue-positive myelin fragments (arrows in J). (K,L) Cerebellar coronal sections from 6-month-old control (K) and mutant (L) mice silver-stained to visualize axonal neurofilaments. When compared with the control (K), there is significant axonal degeneration in the mutant cerebellum (L). Arrowheads in L indicate dystrophic axons. Also obvious in the mutant are macrophages containing silver-positive neurofilament fragments, which are indicative of axonopathy (arrows).





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