The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Deletion of TDP-43 down-regulates Tbc1d1 , a gene linked to obesity, and alters body fat metabolism
Open accessAbstract
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.
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Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
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The ground state of embryonic stem cell self-renewal
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TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Sreedharan, J., Blair, I. P., Tripathi, V. B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J. C., Williams, K. L., Buratti, E., et al. (2008) · Science · doi:10.1126/science.1154584 · Cited by 2,630
TDP-43 Is a Developmentally Regulated Protein Essential for Early Embryonic Development
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Loss of murine TDP-43 disrupts motor function and plays an essential role in embryogenesis
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Self-citationGains or losses: molecular mechanisms of TDP43-mediated neurodegeneration
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Metadata
- Authors
- Chiang, P.-M., Ling, J., Jeong, Y. H., Price, D. L., Aja, S. M., & Wong, P. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2010-07-26
- Volume
- 107
- Issue
- 37
- Pages
- 16320-16324
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2069376224
- Cited by
- 302
- References
- 5
- FWCI
- 9.35
- Type
- journal article
- Language
- en
- Open access
- green
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- 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. https://doi.org/10.1073/pnas.1002176107
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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