Deletion of TDP-43 down-regulates Tbc1d1 , a gene linked to obesity, and alters body fat metabolism
10.1073/pnas.1002176107
Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
Abstract

Tat activating regulatory DNA-binding protein (Tardbp or TDP-43), a highly conserved metazoan DNA/RNA binding protein thought to be involved in RNA transcription and splicing, has been linked to the pathophysiology of amyotrophic lateral sclerosis and frontotemporal lobar degeneration and is essential for early embryonic development. However, neither the physiological role of TDP-43 in the adult nor its downstream targets are well defined. To address these questions, we developed conditional Tardbp -KO mice and embryonic stem (ES) cell models. Here, we show that postnatal deletion of Tardbp in mice caused dramatic loss of body fat followed by rapid death. Moreover, conditional Tardbp -KO ES cells failed to proliferate. Importantly, high-throughput DNA sequencing analysis on the transcriptome of ES cells lacking Tardbp revealed a set of downstream targets of TDP-43. We show that Tbc1d1 , a gene known to mediate leanness and linked to obesity, is down-regulated in the absence of TDP-43. Collectively, our results establish that TDP-43 is critical for fat metabolism and ES cell survival.

Bibliography

Chiang, P.-M., Ling, J., Jeong, Y. H., Price, D. L., Aja, S. M., & Wong, P. C. (2010). Deletion of TDP-43 down-regulates Tbc1d1 , a gene linked to obesity, and alters body fat metabolism. Proceedings of the National Academy of Sciences, 107(37), 16320–16324.

Authors 6
  1. Po-Min Chiang (first)
  2. Jonathan Ling (additional)
  3. Yun Ha Jeong (additional)
  4. Donald L. Price (additional)
  5. Susan M. Aja (additional)
  6. Philip C. Wong (additional)
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Dates
Type When
Created 15 years, 1 month ago (July 26, 2010, 11:41 p.m.)
Deposited 3 years, 2 months ago (June 7, 2022, 2:56 a.m.)
Indexed 43 minutes ago (Sept. 2, 2025, 8:17 p.m.)
Issued 15 years, 1 month ago (July 26, 2010)
Published 15 years, 1 month ago (July 26, 2010)
Published Online 15 years, 1 month ago (July 26, 2010)
Published Print 14 years, 11 months ago (Sept. 14, 2010)
Funders 0

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@article{Chiang_2010, title={Deletion of TDP-43 down-regulates Tbc1d1 , a gene linked to obesity, and alters body fat metabolism}, volume={107}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1002176107}, DOI={10.1073/pnas.1002176107}, number={37}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chiang, Po-Min and Ling, Jonathan and Jeong, Yun Ha and Price, Donald L. and Aja, Susan M. and Wong, Philip C.}, year={2010}, month=jul, pages={16320–16324} }