TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy

Journal article

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 SOD1^G93A 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.

Authors: Turner, B; Bäumer, D; Parkinson, N; Scaber, J; Ansorge, O

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: BMC Neuroscience
• Volume: 9
• Article number: 104
• Publication date: 2008-10-28
• Acceptance date: 2008-10-28
• DOI: 10.1186/1471-2202-9-104
• EISSN: 1471-2202
• Language: English
• Keywords: Amyotrophic Lateral Sclerosis; SOD1G93A Mouse; Spinal Muscular Atrophy; SBTMR; Motor Neuron; Motor Neuron Disease