Efficient induction of motor neuron disease in transgenic G93A SOD1 mice by prion-like seeding

Mutations in superoxide dismutase 1 (SOD1) cause paralysis in familial amyotrophic lateral sclerosis and promote its misfolding into neurotoxic aggregates. Previous studies have shown that mice expressing the ALS-causing G85R variant of SOD1 develop paralysis much faster after intraspinal injection of spinal homogenates from paralyzed G85R SOD1 mice. These findings, and other studies in cell models, established the prionoid templating properties of misfolded mutant SOD1. Previously, however, we noted that the widely used Gur1-G93A SOD1 mice, which express at high levels and develop paralysis by 6 months of age, were resistant to seeding by homogenates from paralyzed G93A mice. A line of G93A mice that express at very low levels (VLE-G93A) were responsive to seeding but at low efficiency. The poor susceptibility of G93A-SOD1 mice to seeding was not what we expected if prion-like propagation is essential to SOD1 ALS pathogenesis. In our prior, studies seeding homogenates from paralyzed G9..., Study Design
The primary goal of the study was to determine whether older VLE G93A-SOD1 mice may be more susceptible to prion-like seeding by intrathecal administration of seeding homogenates. We injected VLE G93A mice with homogenates from paralyzed G93A SOD1 mice or pooled homogenates from paralyzed mice expressing G85R-SOD1 fused to yellow fluorescent protein (YFP) that had been made paralyzed by injection of homogenates from paralyzed G93A SOD1 mice (designated P2-G93A seeding pool). Initially, we challenged 12-month-old mice with both seeding homogenates and then subsequently determined whether younger VLE G93A-SOD1 mice were also susceptible, using the P2-G93A pool. Controls for these experiments included uninjected VLE G93A-SOD1 mice and mice injected with a pooled homogenate from young asymptomatic naïve 2-month-old Line 230 mice (Y230 pool). Pathological analyses of these animals produced image data for Figures 2 - 4 of the accompanying publication.
In prelude to the G93A mouse..., # Data from: Efficient induction of motor neuron disease in transgenic G93A SOD1 mice by prion-like seeding

This repository contains animal metadata and histological image data used in the study.\
All files are organized to ensure **clear traceability between animals, experimental conditions referenced in the manuscript, and figure panels**, while supporting **efficient data access, sharing, and repository submission**.

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## Animal Metadata

The image files are documentation of pathologic features in mice that develop paralysis as a result of the injection of tissue homogenates from paralyzed mice. All animals used in this study are documented an Excel file:

* **Xu_et_al_mouse_list.xlsx**

This Excel file contains **11 tabs**, each corresponding to animals contributing to a specific figure in the manuscript. The Tab names refer to the animals used in generating each figure in publication and the tissue homogenate used to induce early paralysis, listed below. The animals used in Fi..., ,