Differential vulnerability of oculomotor, facial, and hypoglossal nuclei in G86R superoxide dismutase transgenic mice

In recent years, several mouse models of amyotrophic lateral sclerosis (ALS) have been developed. One, caused by a G86R mutation in the superoxide dismutase‐1 (SOD‐1) gene associated with familial ALS, has been subjected to extensive quantitative analyses in the spinal cord. However, the human form...

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Bibliographic Details
Published in:Journal of comparative neurology (1911) 2000-01, Vol.416 (1), p.112-125
Main Authors: Nimchinsky, Esther A., Young, Warren G., Yeung, Glendy, Shah, Ravi A., Gordon, Jon W., Bloom, Floyd E., Morrison, John H., Hof, Patrick R.
Format: Article
Language:English
Subjects:
Amino Acid Substitution
amyotrophic lateral sclerosis
Animals
Brain - cytology
Brain - pathology
brainstem motor nuclei
Facial Nerve - cytology
Facial Nerve - pathology
Female
Humans
Hypoglossal Nerve - cytology
Hypoglossal Nerve - pathology
Male
Mice
Mice, Transgenic
motoneuron
Motor Neuron Disease - genetics
Motor Neuron Disease - pathology
neurodegenerative disease
Neurons - cytology
Neurons - pathology
Oculomotor Nerve - cytology
Oculomotor Nerve - pathology
Point Mutation
quantitative neuroanatomy
Reference Values
stereology
Superoxide Dismutase - genetics
transgenic models
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Summary:In recent years, several mouse models of amyotrophic lateral sclerosis (ALS) have been developed. One, caused by a G86R mutation in the superoxide dismutase‐1 (SOD‐1) gene associated with familial ALS, has been subjected to extensive quantitative analyses in the spinal cord. However, the human form of ALS includes pathology elsewhere in the nervous system. In the present study, analyses were extended to three motor nuclei in the brainstem. Mutant mice and control littermates were evaluated daily, and mutants, along with their littermate controls, were killed when they were severely affected. Brains were removed after perfusion and processed for Nissl staining, the samples were randomized, and the investigators were blinded to their genetic status. Stereologic methods were used to estimate the number of neurons, mean neuronal volumes, and nuclear volume in three brainstem motor nuclei known to be differetially involved in the human form of the disease, the oculomotor, facial, and hypoglossal nuclei. In the facial nucleus, neuron number consistently declined (48%), an effect that was correlated with disease severity. The nuclear volume of the facial nucleus was smaller in the SOD‐1 mutant mice (45.7% difference from control mice) and correlated significantly with neuron number. The oculomotor and hypoglossal nuclei showed less extreme involvement (
ISSN:0021-9967
1096-9861
DOI:10.1002/(SICI)1096-9861(20000103)416:1<112::AID-CNE9>3.0.CO;2-K