Presence of Cu/Zn superoxide dismutase (SOD) immunoreactivity in neuronal hyaline inclusions in spinal cords from mice carrying a transgene for Gly93Ala mutant human Cu/Zn SOD |
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Authors: | N Shibata Asao Hirano Makio Kobayashi Mauro C Dal Canto Mark E Gurney Takashi Komori Takahiko Umahara Kohtaro Asayama |
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Institution: | (1) Department of Pathology, Tokyo Women’s Medical College, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan Tel.: 81-3-3353-8111, ext. 22233; Fax: 81-3-5269-7408, JP;(2) Division of Neuropathology, Department of Pathology, Montefiore Medical Center, 111 East 210th Street, Bronx, NY 10467, USA, US;(3) Department of Pathology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA, US;(4) Department of Cell, Molecular and Structural Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA, US;(5) Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183, Japan, JP;(6) Department of Geriatrics, Tokyo Medical College, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160, Japan, JP;(7) Department of Pediatrics, Yamanashi Medical College, 1110 Shimokato, Tamaho-cho, Nakakoma-gun, Yamanashi 409-38, Japan, JP |
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Abstract: | This investigation deals with the immunocytochemical localization of Cu/Zn superoxide dismutase (SOD) in the spinal cord
neurons of transgenic mice that overexpress Gly93Ala mutant human Cu/Zn SOD and demonstrate clinicopathological features similar
to human amyotrophic lateral sclerosis (ALS) with Cu/Zn SOD mutation. At low magnification of light microscopy, the gray and
white matter of the spinal cord of Gly93Ala mice showed more intense Cu/Zn SOD immunoreactivity than that of control mice.
At higher magnification, the cytoplasm of control mice neurons displayed a distinct staining for Cu/Zn SOD, whereas the surrounding
neuropil was only weakly stained. In contrast, the intensity of Cu/ Zn SOD immunoreactivity in the cytoplasm of the majority
of Gly93Ala mice neurons was similar to that in the neuropil. Almost all neuronal hyaline inclusions (NHIs) of Gly93Ala mice
were positively immunostained by antibodies to Cu/Zn SOD, ubiquitin and phosphorylated neurofilament protein (NFP), the intensities
of which were much higher in the NHIs than in the surrounding cytoplasm. In control mice, significant Cu/Zn SOD precipitation
was not observed to be limited to any particular region of the neuronal cytoplasm. Intracytoplasmic vacuoles in the neuronal
soma and processes of Gly93Ala mice were not stained by any of these antibodies. These results indicate that Cu/Zn SOD colocalizes
with ubiquitin and phosphorylated NFP in NHIs of mice expressing mutant Cu/Zn SOD; similar findings have been shown for Lewy
body-like inclusions of familial ALS patients with Cu/Zn SOD mutation. Moreover, our results point to the possibility that
Cu/Zn SOD mutation may have a role in the abnormal Cu/Zn SOD accumulation in the NHIs, in association with motor neuron degeneration.
Received:16 July 1997 / Revised, accepted: 25 September 1997 |
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Keywords: | Amyotrophic lateral sclerosis Transgenic mouse model Superoxide dismutase Hyaline inclusions Immunocytochemistry |
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