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• W2600718316 abstract "Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43Q331K mice develop age- and mutant-dependent motor deficits from degeneration and death of motor neurons. Cre-recombinase-mediated excision of the TDP-43Q331K gene from motor neurons is shown to delay onset of motor symptoms and appearance of TDP-43-mediated aberrant nuclear morphology, and abrogate subsequent death of motor neurons. However, reduction of mutant TDP-43 selectively in motor neurons did not prevent age-dependent degeneration of axons and neuromuscular junction loss, nor did it attenuate astrogliosis or microgliosis. Thus, disease mechanism is non-cell autonomous with mutant TDP-43 expressed in motor neurons determining disease onset but progression defined by mutant acting within other cell types." @default.
• W2600718316 created "2017-04-07" @default.
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• W2600718316 date "2017-03-29" @default.
• W2600718316 modified "2023-10-18" @default.
• W2600718316 title "Mutant TDP-43 within motor neurons drives disease onset but not progression in amyotrophic lateral sclerosis" @default.
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• W2600718316 doi "https://doi.org/10.1007/s00401-017-1698-6" @default.
• W2600718316 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5427168" @default.
• W2600718316 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28357566" @default.
• W2600718316 hasPublicationYear "2017" @default.
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