TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy
Open Access
- 28 October 2008
- journal article
- Published by Springer Science and Business Media LLC in BMC Neuroscience
- Vol. 9 (1), 104
- https://doi.org/10.1186/1471-2202-9-104
Abstract
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). 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. 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.Keywords
This publication has 32 references indexed in Scilit:
- Anterior horn cells with abnormal TDP-43 immunoreactivities show fragmentation of the Golgi apparatus in ALSJournal of the Neurological Sciences, 2008
- TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosisNature Genetics, 2008
- TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral SclerosisScience, 2008
- TDP‐43 A315T mutation in familial motor neuron diseaseAnnals of Neurology, 2008
- Epidemiology and clinical features of amyotrophic lateral sclerosis in Ireland between 1995 and 2004Journal of Neurology, Neurosurgery & Psychiatry, 2008
- Genetics of sporadic amyotrophic lateral sclerosisHuman Molecular Genetics, 2007
- TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin InclusionsThe American Journal of Pathology, 2007
- Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral SclerosisScience, 2006
- Incidence of amyotrophic lateral sclerosis in southern Italy: a population based studyJournal of Neurology, Neurosurgery & Psychiatry, 2005
- Identification and characterization of a spinal muscular atrophy-determining geneCell, 1995