FIGURE

Figure 2

ID

ZDB-FIG-240513-130

Publication

Pokrishevsky et al., 2024 - Tryptophan residues in TDP-43 and SOD1 modulate the cross-seeding and toxicity of SOD1

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Figure 2

Tryptophan residues in human SOD1 and TDP-43 proteins mediate their synergistic impact on motor neuron pathology in vivo.A, mnx1:GFP zebrafish (36 hpf, hours post-fertilization) expressing GFP in the motor neurons. Abnormal primary axons (arrowheads) with branches above the ventral notochord (dashed line). Muscle actin counterstained in magenta. Scale bars represent 0.5 mm (top left and top right); 200 μm (bottom four panels). B, human WT SOD1 and WT TDP-43 synergistically induce primary motor neuron axonopathy. Ser68 and Ser172 TDP-43 mutations reduced SOD1-TDP-43–induced axonopathy (p = 3.57 × 10⁻⁵). The SOD1 Trp32Ser mutation also abrogated axonopathy (p = 4.54 × 10⁻⁵) and in combination with Trpless-TDP-43 (p = 8.94 × 10⁻⁵). Error bars indicate SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001 (Kruskall–Wallis test with Mann–Whitney pairwise comparisons): sample sizes are noted at the base of each bar. Mnx1, motor neuron and pancreas homeobox protein 1; SOD1, superoxide dismutase; TDP, TAR DNA-binding protein.

Expression Data

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Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

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