Mutations in the superoxide dismutase 1 (SOD1) gene are associated with familial amyotrophic lateral sclerosis (ALS), and the SOD1G93A transgenic mouse has been widely used as one animal model for studies of this neurodegenerative disorder. Recently, several reports have shown that abnormalities in neuronal development in other models of neurodegeneration occur much earlier than previously thought. To study the role of mutant SOD1 in glial progenitor biology, we immortalized glial restricted precursors (GRIPs) derived from mouse E11.5 neural tubes of wild-type and SOD1G93A mutant mice. Immunocytochemistry using cell lineage markers shows that these cell lines can be maintained as glial progenitors, because they continue to express A2B5, with very low levels of glial fibrillary acidic protein (astrocyte), βIII-tubulin (neuron), and undetected GalC (oligodendrocyte) markers. RT-PCR and immunoblot analyses indicate that the chemokine receptor CXCR4 is reduced in SOD1G93A GRIPs. Subsequently, SOD1G93A GRIPs are unable to respond to SDF1α to activate ERK1/2 enzymes and the transcription factor CREB. This may be one pathway leading to a reduction in SOD1G93A cell migration. These data indicate that the abnormalities in SOD1G93A glial progenitor expression of CXCR4 and its mediated signaling and function occur during spinal cord development and highlight nonneuronal (glial) abnormalities in this ALS model.
- ERK activation
- Neural progenitors
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience