Neuron-Specific Expression of Mutant Superoxide Dismutase 1 in Transgenic Mice Does Not Lead to Motor Impairment
Open accessAbstract
Mutations were identified in the Cu/Zn superoxide dismutase gene (SOD1) in ∼15% of patients with familial amyotrophic lateral sclerosis. Transgenic animals expressing mutant SOD1 in all tissues develop an ALS-like phenotype. To determine whether neuron-specific expression of mutant SOD1 is sufficient to produce such a phenotype, we generated transgenic animals carrying the G37R mutation that is associated with the familial form of ALS (FALS), which is driven by the neurofilament light chain promoter. The transgenic animals express high levels of the human SOD1 protein in neuronal tissues, especially in the large motor neurons of the spinal cord, but they show no apparent motor deficit at up to 1.5 years of age. Our animal model suggests that neuron-specific expression of ALS-associated mutant human SOD1 may not be sufficient for the development of the disease in mice.
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Neuron-specific expression of mSOD1 in transgenic mice failed to produce pathology or disease.
“However, neuron-specific expression of mSOD1 in transgenic mice failed to produce pathology or disease in these mice,328,329”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [328]
Non-cell-autonomous factors, possibly from non-neuronal cells such as microglia, play a role in ALS pathogenesis.
“suggesting a role of non-cell-autonomous factors, possibly from non-neuronal cells such as microglia, in ALS pathogenesis.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [328]
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- Authors
- Pramatarova, A., Laganière, J., Roussel, J., Brisebois, K., & Rouleau, G. A.
- Affiliations
- Montreal General Hospital (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-05-15
- Volume
- 21
- Issue
- 10
- Pages
- 3369-3374
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6762496
- OpenAlex
- W2124976615
- Cited by
- 482
- References
- 30
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 14 · 2023: 18 · 2022: 14 · 2021: 8 · 2020: 13 · 2019: 15 · 2018: 15 · 2017: 16 · 2016: 15 · 2015: 13 · 2014: 14 · 2013: 24 · 2012: 27
- FWCI
- 15.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Muscular Dystrophy Association
- McGill University
- Medical Research Council Canada
- Medical Research Council
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- superoxide dismutase 1, familial ALS, neuron-specific expression, transgenic mice, motor neurons, motor impairment
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Brain, Disease Models, Animal, Enzyme Activation, Genes, Dominant, Humans, Immunohistochemistry, Mice, Transgenic, Motor Activity, Motor Neurons, Mutation, Organ Specificity, Phenotype, Promoter Regions, Genetic, Spinal Cord, Superoxide Dismutase, Gene Expression, Neurofilament Proteins, Disease Progression, Transgenes, Amino Acid Substitution, Mice
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