Loss of nuclear TDP-43 in ALS causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurons [fibroblasts]

ABSTRACT: Aims: Loss of nuclear TDP-43 characterises sporadic and most familial forms of amyotrophic lateral sclerosis (ALS). TDP-43 (encoded by TARDBP) has multiple roles in RNA processing. We aimed to determine whether 1) RNA splicing dysregulation is present in lower motor neurons in ALS and in a motor neuron-like cell model, and 2) TARDBP mutations (mtTARDBP) are associated with aberrant RNA splicing using patient-derived fibroblasts. Methods: Affymetrix exon arrays were used to study mRNA expression and splicing in lower motor neurons obtained by laser capture microdissection of autopsy tissue from individuals with sporadic ALS and TDP-43 proteinopathy. Findings were confirmed by qRT-PCR and in NSC34 motor neuronal cells following shRNA-mediated TDP-43 depletion. Exon arrays and immunohistochem

ORGANISM(S): Homo sapiens

SUBMITTER: Paul Heath 

PROVIDER: E-GEOD-33855 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress