Characterization of a Novel SOD-1(G93A) Transgenic Mouse Line with Very Decelerated Disease Development
Open Access
- 11 November 2010
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 5 (11), e15445
- https://doi.org/10.1371/journal.pone.0015445
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a fatal motoneuron disease, characterized by progressive weakness, muscle wasting and death ensuing 3–5 years after diagnosis. The etiology of ALS is complex and therapeutic approaches rely mostly on transgenic animal models with SOD-1 mutations. Most frequently employed is a mouse line transgenic for SOD-1 (SOD-1 Tg) that contains a point mutation at amino acid position 93 (G->A), present in patients suffering from a familial form of amyotrophic lateral sclerosis. Here we report on a SOD-1 (G93A) Tg mouse line with abnormally delayed onset of disease and prolonged survival. This phenotype arose spontaneously in our colony of the classic SOD-1 (G93A) line. We found that the copy number of the SOD-1 transgene was drastically decreased. We established a new breeding colony, the SOD-1 (G93A)PS line (PS for prolonged survival) where the phenotype is stably inherited for 4 generations now. The mice develop symptoms at an age of approximately 12 months and die at 15 months of age. The delayed development of disease may more closely mimic human pathophysiology, and studying drug effects in this model may yield added confidence for potential efficacy of ALS drug candidates.This publication has 13 references indexed in Scilit:
- Neurotrophic growth factors for the treatment of amyotrophic lateral sclerosis: where do we stand ?Frontiers in Neuroscience, 2010
- Early Excitability Changes in Lumbar Motoneurons of Transgenic SOD1G85Rand SOD1G93A-LowMiceJournal of Neurophysiology, 2009
- Granulocyte-colony stimulating factor improves outcome in a mouse model of amyotrophic lateral sclerosisBrain, 2008
- Design, power, and interpretation of studies in the standard murine model of ALSAmyotrophic Lateral Sclerosis, 2008
- Amyotrophic lateral sclerosisThe Lancet, 2007
- Effect of transgene copy number on survival in the G93A SOD1 transgenic mouse model of ALSMolecular Brain Research, 2004
- Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: Benefit of a high-energy diet in a transgenic mouse modelProceedings of the National Academy of Sciences of the United States of America, 2004
- Presymptomatic motor neuron loss and reactive astrocytosis in the SOD1 mouse model of amyotrophic lateral sclerosisMuscle & Nerve, 2001
- Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions.Proceedings of the National Academy of Sciences of the United States of America, 1996
- Superoxide DismutasesPublished by Wiley ,1986