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• W2019430733 abstract "In this study, we identified and characterized an N-ethyl-N-nitrosourea (ENU) induced mutation in Usp14 (nmf375) that leads to adult-onset neurological disease. The nmf375 mutation causes aberrant splicing of Usp14 mRNA, resulting in a 95% reduction in USP14. We previously showed that loss of USP14 in ataxia (axJ) mice results in reduced ubiquitin levels, motor endplate disease, Purkinje cell axonal dystrophy and decreased hippocampal paired pulse facilitation (PPF) during the first 4-6 weeks of life, and early postnatal lethality by two months of age. Although the loss of USP14 is comparable between the nmf375 and axJ mice, the nmf375 mice did not exhibit these axJ developmental abnormalities. However, by 12 weeks of age the nmf375 mutants present with ubiquitin depletion and motor endplate disease, indicating a continual role for USP14-mediated regulation of ubiquitin pools and neuromuscular junction (NMJ) structure in adult mice. The observation that motor endplate disease was only seen after ubiquitin depletion suggests that the preservation of NMJ structure requires the stable maintenance of synaptic ubiquitin pools. Differences in genetic background were shown to affect ubiquitin expression and dramatically alter the phenotypes caused by USP14 deficiency." @default.
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• W2019430733 date "2013-12-16" @default.
• W2019430733 modified "2023-09-30" @default.
• W2019430733 title "Genetic Background Alters the Severity and Onset of Neuromuscular Disease Caused by the Loss of Ubiquitin-Specific Protease 14 (Usp14)" @default.
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• W2019430733 doi "https://doi.org/10.1371/journal.pone.0084042" @default.
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