Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons ofTDP-43transgenic mice
10.1073/pnas.1003459107
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

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 intranuclear inclusions composed of TDP-43 and fused in sarcoma/translocated in liposarcoma (FUS/TLS), 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 an 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 a decrease in abundance of neurofilament transcripts contributed to the reduction of caliber of motor axons inTDP-43mice. 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.

Bibliography

Shan, X., Chiang, P.-M., Price, D. L., & Wong, P. C. (2010). Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons ofTDP-43transgenic mice. Proceedings of the National Academy of Sciences, 107(37), 16325–16330.

Authors 4
  1. Xiu Shan (first)
  2. Po-Min Chiang (additional)
  3. Donald L. Price (additional)
  4. Philip C. Wong (additional)
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Dates
Type When
Created 15 years ago (Aug. 24, 2010, 9:58 p.m.)
Deposited 1 year, 5 months ago (March 29, 2024, 5:27 p.m.)
Indexed 1 day, 22 hours ago (Aug. 30, 2025, 1:19 p.m.)
Issued 15 years ago (Aug. 24, 2010)
Published 15 years ago (Aug. 24, 2010)
Published Online 15 years ago (Aug. 24, 2010)
Published Print 14 years, 11 months ago (Sept. 14, 2010)
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