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Thin corpus callosum and axonal spheroids in the brain of AP-4 ε KO mice.

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posted on 2018-04-26, 18:13 authored by Raffaella De Pace, Miguel Skirzewski, Markus Damme, Rafael Mattera, Jeffrey Mercurio, Arianne M. Foster, Loreto Cuitino, Michal Jarnik, Victoria Hoffmann, H. Douglas Morris, Tae-Un Han, Grazia M. S. Mancini, Andrés Buonanno, Juan S. Bonifacino

(A) MRI shows thinner corpus callosum (arrowheads and green highlights) in the brain of a 9-month-old KO relative to an age-matched WT mouse. Results are representative of three mice per group. (B) Coronal brain sections stained with H&E show ~55% thinner corpus callosum in a 9-month-old KO mouse relative to an aged-matched WT mouse. Bars: 500 μm. The thickness of the corpus callosum in comparable sections is indicated. Results are representative of two mice per group. (C,D) H&E staining of coronal sections of brains from 9-month-old mice show the appearance of both weakly and strongly stained spheroids (arrowheads) in deep cerebellar nuclei (DCN) of KO but not WT mice. The numbered panels are four-fold magnifications of the boxed areas. Bars: 20 μm. (E,F) Immunohistochemical staining for calbindin (green) in sections from the cerebellum shows rare axonal spheroids in the proximal axons of Purkinje neurons (E) and numerous spheroids in distal axons of Purkinje neurons in DCN (F) of KO mice but not WT mice. Spheroids are indicated by arrowheads. Bars: 50 μm. (G) Immunohistochemical co-staining for calbindin (green) and LAMP1 (red) of sections from the cerebellum show that Purkinje cells spheroids in DCN from KO mice are negative for LAMP1 (arrowheads). Bars: 50 μm. (H) Immunohistochemical co-staining for the neurofilament protein NFH (green) and LAMP1 (red) of sections from midbrain white matter tracts show spheroids containing both proteins (arrowheads) in KO mice. Bars: 50 μm. In G and H, single-channel images are shown in inverted grayscale. In E-H, DAPI (blue) was used to stain the nuclei.

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