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• W2103444316 abstract "The G59S missense mutation at the conserved microtubule-binding domain of p150 glued , a major component of dynein/dynactin complex, has been linked to an autosomal dominant form of motor neuron disease (MND). To study how this mutation affects the function of the dynein/dynactin complex and contributes to motor neuron degeneration, we generated p150 glued G59S knock-in mice. We found that the G59S mutation destabilizes p150 glued and disrupts the function of dynein/dynactin complex, resulting in early embryonic lethality of homozygous knock-in mice. Heterozygous knock-in mice, which developed normally, displayed MND-like phenotypes after 10 months of age, including excessive accumulation of cytoskeletal and synaptic vesicle proteins at neuromuscular junctions, loss of spinal motor neurons, increase of reactive astrogliosis, and shortening of gait compared with wild-type littermates and age-matched p150 glued heterozygous knock-out mice. Our findings indicate that the G59S mutation in p150 glued abrogates the normal function of p150 glued and accelerates motor neuron degeneration." @default.
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• W2103444316 date "2007-12-19" @default.
• W2103444316 modified "2023-10-14" @default.
• W2103444316 title "The G59S Mutation in p150^gluedCauses Dysfunction of Dynactin in Mice" @default.
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• W2103444316 doi "https://doi.org/10.1523/jneurosci.4226-07.2007" @default.
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