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The SOD1<jats:sup>G93A<\/jats:sup> mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125\u2013150\u00a0days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca<jats:sup>2+<\/jats:sup>] ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>), and resting [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> remained unchanged with disease. Fibre\u2010type distribution was maintained in late\u2010stage SOD1<jats:sup>G93A<\/jats:sup> FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1<jats:sup>G93A<\/jats:sup> is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training\u2010like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277456","type":"journal-article","created":{"date-parts":[[2019,5,10]],"date-time":"2019-05-10T04:54:16Z","timestamp":1557464056000},"page":"3133-3146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Intact single muscle fibres from SOD1<sup>G93A<\/sup> amyotrophic lateral sclerosis mice display preserved specific force, fatigue resistance and training\u2010like adaptations"],"prefix":"10.1113","volume":"597","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-2967","authenticated-orcid":false,"given":"Arthur J.","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Karolinska Institutet  171 77 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