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• W2071751113 abstract "Amyotrophic lateral sclerosis (ALS) is an incurable progressive paralytic motor neuron disease with limited therapeutic options. Since their creation by Gurney et al. (1994) [Science 264:1772–1775], transgenic superoxide dismutase-1 with glycine to alanine switch at codon 93 (SOD1G93A) mice have become the benchmark pre-clinical model for screening ALS therapies. Surprisingly, despite physiological, anatomical, ultrastructural and biochemical evidence of early motor system dysfunction, it has proven difficult to detect motor performance deficits in pre-symptomatic SOD1G93A mice. As an alternative to conventional forced motor tests, we investigated the progression of motor performance deficits in freely behaving pre-symptomatic congenic B6.SOD1G93A mice. We found that motor performance deficits began several weeks prior to the onset of overt clinical symptoms (postnatal day 45). More importantly, once motor performance deficits manifested, they persisted in parallel with disease progression. In addition, two physical measures of muscle girth revealed progressive hindlimb muscle atrophy that predicted genotype in individual pre-symptomatic mice with 80% accuracy. Together, these data suggest that muscle girth is a reliable and indirect measure of hindlimb muscle denervation and an early, objective marker for disease onset in congenic B6.SOD1G93A ALS mice. Moreover, we present regression equations based on hindlimb muscle girth for predicting genotype in future studies using B6.SOD1G93A mice. These findings support new objective criteria for clinical disease onset and provide objective measures that require little expertise. These studies demonstrate a cost-effective approach for more thorough evaluation of neuroprotective strategies that seek to disrupt disease mechanisms early in the disease process. To our knowledge, these findings are the first to report early chronic motor performance and physical deficits that are coincident with the earliest known motor dysfunction in any ALS mouse model." @default.
• W2071751113 created "2016-06-24" @default.
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• W2071751113 date "2009-12-01" @default.
• W2071751113 modified "2023-10-16" @default.
• W2071751113 title "Pre-symptomatic detection of chronic motor deficits and genotype prediction in congenic B6.SOD1G93A ALS mouse model" @default.
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• W2071751113 doi "https://doi.org/10.1016/j.neuroscience.2009.08.031" @default.
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