Neurodegeneration in Lsd1 CAGG mice. a–d LSD1 immunohistochemistry (IHC) of control a, c and Lsd1 CAGG b, d CA1 a, b and cortex c, d. Arrowheads highlight non-pyknotic LSD1 immunoreactive nuclei. Arrows highlight pyknotic LSD1 negative nuclei. e, f Representative images of Lsd1 CAGG mice with the terminal motor defect including hindlimb clasping e and failure to maintain posture f. g The age of each individual male (blue) or female (red) mouse at the final tamoxifen injection (start of each line) to inducibly delete Lsd1, and the number of days (length of the line) until the terminal motor defect is reached. Inset shows survival in days for each sex. Data are shown as mean survival in days ± s.e.m., n = 45 animals h, i H&E staining of tamoxifen injected Cre minus control (control) h and Lsd1 CAGG i CA1 and cortex. Insets are magnified views of non-pyknotic h and pyknotic i nuclei. CC denotes corpus callosum. j–q MAP2 IHC of control j, l, n, p and Lsd1 CAGG k, m, o, q CA1 j, k, CA3 l, m, dentate gyrus n, o and cortex p, q. Brackets highlight dendrites and arrows highlight pyknotic nuclei. r, s Tau IHC of control r and Lsd1CAGG s CA1. Bracket highlights axons. t–w GFAP IHC of control t, v and Lsd1 CAGG u, w hippocampus t, u and cortex v, w. Arrowheads highlight sparse astrocytes in control cortex. Insets show magnified view of representative astrocytes. x−aa Merge of DAPI (red) and TUNEL (green) in control x, z and Lsd1 CAGG y, aa CA1 x, y and cortex z, aa. All IHC j–w is counterstained with hematoxylin. All Lsd1 CAGG images are taken at the terminal phenotype. Scale bar = 50 µm

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