TY - JOUR
T1 - Ultrastructural, morphometric, and immunocytochemical study of anterior hom cells in mice with “wasted” mutation
AU - Lutsep, Helmi L.
AU - Rodriguez, Moses
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1989/9
Y1 - 1989/9
N2 - Mice with the autosomal recessive gene “wasted” (wst/wst) manifest hindlimb paralysis and tremulousness, develop reduced secretory immune responses, and have abnormal DNA repair mechanisms. There is prominent vacuolar degeneration of neurons within anterior horns of the spinal cord and motor nuclei of the brainstem. A morphometric analysis of motor neurons in the spinal cord was performed on 2-hydroxyethyl methacrylate-embedded tissue from ten wst/wst mice, ten littermates (wst/+, +/+) without clinical deficits, and ten parental (+/+) control mice. Vacuolated neurons were present only in wst/wst mice (p=0.0008). Fibrillary neurons were more numerous in the wst/wst mice than in littermates (p=0.01) or controls (p=0.007). The number of total or normal neurons did not differ significantly among the three groups. Volume measurements for normal, fibrillary, vacuolated, and total neurons were greater in wst/wst mice (p<0.008). Electron microscopic studies revealed vacuolar degeneration exclusively within neurons of wst/wst mice with the prominent accumulation of neurofilaments. Immunocytochemical staining of Araldite-embedded sections with monoclonal antibodies (MAb) to 68 kDa, 160 kDa, and 200 kDa neurofilament proteins showed prominent staining of vacuolated and fibrillary neurons in wst/wst mice exclusively with the MAb to 200 kDa neurofilaments. Dephosphorylation of tissue reduced the staining of 200 kDa neurofilaments in wst/ wst mice. These studies suggest that phosphorylated neurofilaments may be important in events producing neuronal dysfunction. Therefore the “wasted” mutation may be an excellent model for the study of motor neuron disease.
AB - Mice with the autosomal recessive gene “wasted” (wst/wst) manifest hindlimb paralysis and tremulousness, develop reduced secretory immune responses, and have abnormal DNA repair mechanisms. There is prominent vacuolar degeneration of neurons within anterior horns of the spinal cord and motor nuclei of the brainstem. A morphometric analysis of motor neurons in the spinal cord was performed on 2-hydroxyethyl methacrylate-embedded tissue from ten wst/wst mice, ten littermates (wst/+, +/+) without clinical deficits, and ten parental (+/+) control mice. Vacuolated neurons were present only in wst/wst mice (p=0.0008). Fibrillary neurons were more numerous in the wst/wst mice than in littermates (p=0.01) or controls (p=0.007). The number of total or normal neurons did not differ significantly among the three groups. Volume measurements for normal, fibrillary, vacuolated, and total neurons were greater in wst/wst mice (p<0.008). Electron microscopic studies revealed vacuolar degeneration exclusively within neurons of wst/wst mice with the prominent accumulation of neurofilaments. Immunocytochemical staining of Araldite-embedded sections with monoclonal antibodies (MAb) to 68 kDa, 160 kDa, and 200 kDa neurofilament proteins showed prominent staining of vacuolated and fibrillary neurons in wst/wst mice exclusively with the MAb to 200 kDa neurofilaments. Dephosphorylation of tissue reduced the staining of 200 kDa neurofilaments in wst/ wst mice. These studies suggest that phosphorylated neurofilaments may be important in events producing neuronal dysfunction. Therefore the “wasted” mutation may be an excellent model for the study of motor neuron disease.
KW - Amyotropic lateral sclerosis
KW - Anterior horn
KW - Morphometry
KW - Motor neurons
KW - Mouse mutant, “Wasted”
KW - Neurofilaments
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U2 - 10.1097/00005072-198909000-00003
DO - 10.1097/00005072-198909000-00003
M3 - Article
C2 - 2475588
AN - SCOPUS:0024458118
SN - 0022-3069
VL - 48
SP - 519
EP - 533
JO - Journal of Neuropathology and Experimental Neurology
JF - Journal of Neuropathology and Experimental Neurology
IS - 5
ER -