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BACKGROUND: Redistribution of nuclear TAR DNA binding protein 43 (TDP-43) to the cytoplasm and ubiquitinated inclusions of spinal motor neurons and glial cells is characteristic of amyotrophic lateral sclerosis (ALS) pathology. Recent evidence suggests that TDP-43 pathology is common to sporadic ALS and familial ALS without SOD1 mutation, but not SOD1-related fALS cases. Furthermore, it remains unclear whether TDP-43 abnormalities occur in non-ALS forms of motor neuron disease. Here, we characterise TDP-43 localisation, expression levels and post-translational modifications in mouse models of ALS and spinal muscular atrophy (SMA). RESULTS: TDP-43 mislocalisation to ubiquitinated inclusions or cytoplasm was notably lacking in anterior horn cells from transgenic mutant SOD1G93A mice. In addition, abnormally phosphorylated or truncated TDP-43 species were not detected in fractionated ALS mouse spinal cord or brain. Despite partial colocalisation of TDP-43 with SMN, depletion of SMN- and coilin-positive Cajal bodies in motor neurons of affected SMA mice did not alter nuclear TDP-43 distribution, expression or biochemistry in spinal cords. CONCLUSION: These results emphasise that TDP-43 pathology characteristic of human sporadic ALS is not a core component of the neurodegenerative mechanisms caused by SOD1 mutation or SMN deficiency in mouse models of ALS and SMA, respectively.

Original publication




Journal article


BMC Neurosci

Publication Date





Amyotrophic Lateral Sclerosis, Animals, Anterior Horn Cells, Cell Nucleus, Coiled Bodies, Cytoplasm, DNA-Binding Proteins, Disease Models, Animal, Female, Inclusion Bodies, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Muscular Atrophy, Spinal, Protein Processing, Post-Translational, Protein Transport, Spinal Cord, Superoxide Dismutase, Survival of Motor Neuron 1 Protein, Ubiquitination