TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy
<p style="text-align:justify;"><b> Background:</b> 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. Rece...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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BioMed Central
2008
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| _version_ | 1797104909607239680 |
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| author | Turner, B Bäumer, D Parkinson, N Scaber, J Ansorge, O Talbot, K |
| author_facet | Turner, B Bäumer, D Parkinson, N Scaber, J Ansorge, O Talbot, K |
| author_sort | Turner, B |
| collection | OXFORD |
| description | <p style="text-align:justify;"><b> Background:</b> 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). <br/><br/> <b>Results:</b> TDP-43 mislocalisation to ubiquitinated inclusions or cytoplasm was notably lacking in anterior horn cells from transgenic mutant SOD1<sup>G93A</sup> 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. <br/><br/> <b>Conclusion:</b> 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. </p> |
| first_indexed | 2024-03-07T06:40:07Z |
| format | Journal article |
| id | oxford-uuid:f8fbc96c-21e0-4a12-85df-1388c2474287 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:40:07Z |
| publishDate | 2008 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:f8fbc96c-21e0-4a12-85df-1388c24742872022-03-27T12:54:34ZTDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f8fbc96c-21e0-4a12-85df-1388c2474287EnglishSymplectic Elements at OxfordBioMed Central2008Turner, BBäumer, DParkinson, NScaber, JAnsorge, OTalbot, K <p style="text-align:justify;"><b> Background:</b> 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). <br/><br/> <b>Results:</b> TDP-43 mislocalisation to ubiquitinated inclusions or cytoplasm was notably lacking in anterior horn cells from transgenic mutant SOD1<sup>G93A</sup> 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. <br/><br/> <b>Conclusion:</b> 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. </p> |
| spellingShingle | Turner, B Bäumer, D Parkinson, N Scaber, J Ansorge, O Talbot, K TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy |
| title | TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy |
| title_full | TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy |
| title_fullStr | TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy |
| title_full_unstemmed | TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy |
| title_short | TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy |
| title_sort | tdp 43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy |
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