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• W4386221413 endingPage "1819" @default.
• W4386221413 startingPage "1819" @default.
• W4386221413 abstract "Mutations in superoxide dismutase 1 (SOD1) that are associated with amyotrophic lateral sclerosis (ALS) cause its misfolding and aggregation. Prior studies have demonstrated that the misfolded conformation of ALS-SOD1 can template with naïve SOD1 “host proteins” to propagate, spread, and induce paralysis in SOD1 transgenic mice. These observations have advanced the argument that SOD1 is a host protein for an ALS conformer that is prion-like and experimentally transmissible. Here, we investigated the propagation of different isolates of G93A-SOD1 ALS conformers using a paradigm involving transmission to mice expressing human G85R-SOD1 fused to yellow fluorescent protein (G85R-SOD1:YFP). In these studies, we also utilized a newly developed line of mice in which the G85R-SOD1:YFP construct was flanked by loxp sites, allowing its temporal and spatial regulation. We used methods in which the G93A ALS conformers were injected into the sciatic nerve or hindlimb muscle of adult transgenic mice. We observed that the incubation period to paralysis varied significantly depending upon the source of inoculum containing misfolded G93A SOD1. Serial passage and selection produced stable isolates of G93A ALS conformers that exhibited a defined minimum incubation period of ~2.5 months when injected into the sciatic nerve of young adult mice. As expected, neuronal excision of the transgene in loxpG85R-SOD1:YFP mice blocked induction of paralysis by transmission of G93A ALS conformers. Our findings indicate that G93A ALS conformers capable of inducing disease require neuronal expression of a receptive host SOD1 protein for propagation, with a defined incubation period to paralysis." @default.
• W4386221413 created "2023-08-29" @default.
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• W4386221413 date "2023-08-26" @default.
• W4386221413 modified "2023-09-30" @default.
• W4386221413 title "Multiple Factors Influence the Incubation Period of ALS Prion-like Transmission in SOD1 Transgenic Mice" @default.
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• W4386221413 doi "https://doi.org/10.3390/v15091819" @default.
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• W4386221413 hasPublicationYear "2023" @default.
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