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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 31, 2010 |
| Title |
Altered Distributions of SMN-containing GEMs and Mitochondria in Motor Neurons of TDP-43 transgenic Mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
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
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| Contributor(s) |
Shan X, Chiang P, Price DL, Wong PC |
| Citation(s) |
20736350 |
| Submission date |
Jun 15, 2010 |
| Last update date |
May 15, 2019 |
| Contact name |
Jonathan Ling |
| E-mail(s) |
jling@jhu.edu
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| Phone |
4105025189
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| Organization name |
Johns Hopkins University
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| Department |
Neuropathology
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| Lab |
Philip Wong
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| Street address |
720 Rutland Ave.
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| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
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| Platforms (1) |
| GPL9185 |
Illumina Genome Analyzer (Mus musculus) |
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| Samples (6)
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| Relations |
| SRA |
SRP002623 |
| BioProject |
PRJNA127491 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE22351_RAW.tar |
4.6 Gb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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