Dataset Information

RNA-seq of mouse spinal cord expressing wild type human TDP-43

ABSTRACT: TDP-43, a DNA/RNA binding protein involved in RNA transcription and splicing has been associated with the pathophysiology of neurodegenerative diseases, including ALS. However, the function of TDP-43 in motor neurons remains undefined. Here, we employ both gain- and loss-of-function approaches to determine roles of TDP-43 in motor neurons. Mice expressing human TDP-43 in neurons exhibited growth retardation and premature death that are characterized by abnormal intranuclear inclusions comprised of TDP-43 and Fused in Sarcoma (FUS), and massive accumulation of mitochondria in TDP-43-negative cytoplasmic inclusions in motor neurons, lack of mitochondria in motor axon terminals and immature neuromuscular junctions. Whereas elevated level of TDP-43 disrupts the normal nuclear distribution of Survival Motor Neuron (SMN)-associated Gemini of coiled bodies (GEMs) in motor neurons, its absence prevents the formation of GEMs in the nuclei of these cells. Moreover, transcriptome-wide deep sequencing analysis revealed that decrease in abundance of neurofilament transcripts contributed to the reduction of caliber of motor axons in TDP-43 mice. In concert, our findings indicate that TDP-43 participates in pathways critical for motor neuron physiology, including those that regulate the normal distributions of SMN-associated GEMs in the nucleus and mitochondria in the cytoplasm. Human TDP-43 coding region were inserted into pThy1.2 expression cassette and subsequently injected into C57BL/6;SJL hybrid mouse embryos to make human TDP-43 transgenic mice

REANALYSED by: E-GEOD-22351

ORGANISM(S): Mus musculus

SUBMITTER: Xiu Shan Jonathan Ling Po-Min Chiang Philip C Wong Donald L Price

PROVIDER: E-GEOD-22351 | ArrayExpress | 2010-07-30

SECONDARY ACCESSION(S): SRP002623GSE22351PRJNA127491

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice.

Shan Xiu X Chiang Po-Min PM Price Donald L DL Wong Philip C PC

Proceedings of the National Academy of Sciences of the United States of America 20100824 37

TAR DNA-binding protein-43 (TDP-43), a DNA/RNA-binding protein involved in RNA transcription and splicing, has been associated with the pathophysiology of neurodegenerative diseases, including ALS. However, the function of TDP-43 in motor neurons remains undefined. Here we use both gain- and loss-of-function approaches to determine roles of TDP-43 in motor neurons. Mice expressing human TDP-43 in neurons exhibited growth retardation and premature death that are characterized by abnormal intranuc ...[more]

PMID: 20736350

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