Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice

摘要: Dominant mutations in ubiquitously expressed superoxide dismutase (SOD1) cause familial ALS by provoking premature death of adult motor neurons. To test whether mutant damage to cell types beyond neurons is required for the onset neuron disease, we generated chimeric mice which all and oligodendrocytes SOD1 at a level sufficient fatal, early-onset disease when ubiquitously, but did so cellular environment containing variable numbers non-mutant, non-motor Despite high-level expression within 100% oligodendrocytes, most these chimeras, presence WT substantially delayed degeneration, increasing disease-free life 50%. Disease therefore non-cell autonomous, other than central contributor initiation degeneration.