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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: A robust TDP-43 knock-in mouse model of ALS

Fig. 3

Patho-signature analysis of TDP-43 in spinal cord of N390D/+ knock-in male mice. a Expression of TDP-43 in different tissues of 6-month old A315T/+ (left panel) and N390D/+ male mice (right panel). Statistical analysis is shown in the box plots (min to max with all points). b Expression of TDP-43 (including TDP-35 and TDP-25) in the soluble and insoluble fractions of spinal cord. The relative fold of total spinal cord TDP-43 is exemplified in the right upper box plots (with all points). The lower stacked bar plot (mean ± SD) indicates the proportions of soluble and insoluble TDP-43 in the spinal cord of +/+ and N390D/+ male mice. c Immunofluorescence co-staining of spinal cord lumbar sections from +/+ and N390D/+ male mice using anti-TDP-43 (green), anti-ubiquitin (Ub, gray) and anti-ChAT (red; a motor neuron marker). DAPI (blue) indicates the locations of the nuclei. Image of the motor neurons are magnified from the ventral horn of the spinal cord. The vessel-like signals are likely due to staining of axons of the motor neurons. The white line boxes in the first column indicate the magnified regions of panels on the right. The scale bars are 50 μm. d Statistical comparison of the ChAT (+) motor neuron numbers per section, the % of ubiquitin (+) MN among the ChAT (+) MN, and the % of ChAT (+) MN with large ubiquitin (+) TDP-43 (+) MN aggregates. e The cytosolic and nuclear distribution of spinal cord TDP-43 in the N390D/+ and +/+ male mice at different ages. Histone H4 (nuclear marker) and ɑ-tubulin (cytosolic marker) were used to validate the fractionation of cellular extracts. The scatter plot (mean ± SD) deduced from the Western blotting data are shown below the blots. N = 6 (3 mice from each of the two independent lines) per group in a, b and e. N3 (randomly chosen from each of the two independent lines) per group in c and d. Significantly different represented in a-e: *p < 0.05, **p < 0.01, #p < 0.001

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