Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14)

• Published in: PloS one Vol. 8; no. 12; p. e84042
• Main Authors: Marshall, Andrea G, Watson, Jennifer A, Hallengren, Jada J, Walters, Brandon J, Dobrunz, Lynn E, Francillon, Ludwig, Wilson, Julie A, Phillips, Scott E, Wilson, Scott M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.12.2013; Public Library of Science (PLoS)
• Subjects: Aberration; Abnormalities; Alternative Splicing; Amyotrophic lateral sclerosis; Animals; Ataxia; Axons - pathology; Base Sequence; Brain research; Chromosome Mapping; Depletion; Disease Models, Animal; Dystrophy; Enzymes; Ethyl nitrosourea; Gene Expression; Genetic aspects; Hippocampus; Hippocampus - metabolism; Homeostasis - genetics; Humans; Kinases; Laboratory animals; Lethality; Mice; Motor Endplate - metabolism; Motor Endplate - pathology; mRNA; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; Mutants; Mutation; Nervous system; Nervous system diseases; Neurobiology; Neuromuscular Diseases - enzymology; Neuromuscular Diseases - genetics; Neuromuscular Diseases - mortality; Neuromuscular Junction - metabolism; Neuromuscular Junction - pathology; Neuromuscular junctions; Neuronal Plasticity; Neurophysiology; Neurosciences; Phenotype; Pools; Preservation; Proteases; Protein Subunits - genetics; Proteins; Purkinje Cells - cytology; Purkinje Cells - metabolism; Receptors, Cholinergic - chemistry; Receptors, Cholinergic - genetics; RNA; RNA, Messenger - chemistry; RNA, Messenger - genetics; Severity of Illness Index; Splicing; Synapses - metabolism; Ubiquitin; Ubiquitin - genetics; Ubiquitin - metabolism; Ubiquitin Thiolesterase - deficiency; Ubiquitin Thiolesterase - genetics; Ubiquitin-specific proteinase; Alabama; United States > US

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...