Journal
NATURE NEUROSCIENCE
Volume 10, Issue 5, Pages 608-614Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn1885
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Funding
- NICHD NIH HHS [R01 HD046732, R01 HD046732-01A1] Funding Source: Medline
- NINDS NIH HHS [R01 NS043915-27, R01 NS043915] Funding Source: Medline
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Here we report an in vitro model system for studying the molecular and cellular mechanisms that underlie the neurodegenerative disease amyotrophic lateral sclerosis ( ALS). Embryonic stem cells ( ESCs) derived from mice carrying normal or mutant transgenic alleles of the human SOD1 gene were used to generate motor neurons by in vitro differentiation. These motor neurons could be maintained in long-term coculture either with additional cells that arose during differentiation or with primary glial cells. Motor neurons carrying either the nonpathological human SOD1 transgene or the mutant SOD1G93A allele showed neurodegenerative properties when cocultured with SOD1G93A glial cells. Thus, our studies demonstrate that glial cells carrying a human SOD1G93A mutation have a direct, non - cell autonomous effect on motor neuron survival. More generally, our results show that ESC- based models of disease provide a powerful tool for studying the mechanisms of neural degeneration. These phenotypes displayed in culture could provide cell- based assays for the identification of new ALS drugs.
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