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Transgenic Rescue ofataxiaMice with Neuronal-Specific Expression of Ubiquitin-Specific Protease 14

Publication ,  Journal Article
Crimmins, S; Jin, Y; Wheeler, C; Huffman, AK; Chapman, C; Dobrunz, LE; Levey, A; Roth, KA; Wilson, JA; Wilson, SM
Published in: The Journal of Neuroscience
November 1, 2006

Themutation () is a recessive neurological mutation that results in reduced growth, ataxia, and hindlimb muscle wasting in mice. Thegene encodes ubiquitin-specific protease 14 (), a deubiquitinating enzyme (DUB) that associates with the proteasome via its ubiquitin-like (Ubl) domain and is involved in processing ubiquitin chains. Analysis ofgene products demonstrated thatundergoes alternative pre-mRNA splicing to produce a full-length form of Usp14 that is capable of binding proteasomes and a form that contains a deletion in the Ubl domain. The full-length form of Usp14 is the only form that appears to be reduced in themice. Transgenic rescue of themice with neuronal-specific expression of Usp14 demonstrated that the full-length form of Usp14 was sufficient to restore viability and motor system function to themice. Biochemical analysis showed that the ubiquitin hydrolyase activity of this form of Usp14 is dependent on the presence of proteasomes, and neuronal expression of full-length Usp14 was able to restore the levels of monomeric ubiquitin in the brains ofmice. However, the-rescued mice still displayed the Purkinje cell axonal swellings that are seen in themice, indicating that this cerebellar alteration is not the primary cause of themovement disorders. These results show that the motor defects observed in themice are attributable to a neuropathic disease rather than to a muscular disorder and suggest that changes in proteasomal function may contribute to neurological dysfunction in themice.

Duke Scholars

Published In

The Journal of Neuroscience

DOI

EISSN

1529-2401

ISSN

0270-6474

Publication Date

November 1, 2006

Volume

26

Issue

44

Start / End Page

11423 / 11431

Publisher

Society for Neuroscience

Related Subject Headings

  • Neurology & Neurosurgery
  • 17 Psychology and Cognitive Sciences
  • 11 Medical and Health Sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Crimmins, S., Jin, Y., Wheeler, C., Huffman, A. K., Chapman, C., Dobrunz, L. E., … Wilson, S. M. (2006). Transgenic Rescue ofataxiaMice with Neuronal-Specific Expression of Ubiquitin-Specific Protease 14. The Journal of Neuroscience, 26(44), 11423–11431. https://doi.org/10.1523/jneurosci.3600-06.2006
Crimmins, Stephen, Youngam Jin, Crystal Wheeler, Alexis K. Huffman, Carlene Chapman, Lynn E. Dobrunz, Alan Levey, Kevin A. Roth, Julie A. Wilson, and Scott M. Wilson. “Transgenic Rescue ofataxiaMice with Neuronal-Specific Expression of Ubiquitin-Specific Protease 14.” The Journal of Neuroscience 26, no. 44 (November 1, 2006): 11423–31. https://doi.org/10.1523/jneurosci.3600-06.2006.
Crimmins S, Jin Y, Wheeler C, Huffman AK, Chapman C, Dobrunz LE, et al. Transgenic Rescue ofataxiaMice with Neuronal-Specific Expression of Ubiquitin-Specific Protease 14. The Journal of Neuroscience. 2006 Nov 1;26(44):11423–31.
Crimmins, Stephen, et al. “Transgenic Rescue ofataxiaMice with Neuronal-Specific Expression of Ubiquitin-Specific Protease 14.” The Journal of Neuroscience, vol. 26, no. 44, Society for Neuroscience, Nov. 2006, pp. 11423–31. Crossref, doi:10.1523/jneurosci.3600-06.2006.
Crimmins S, Jin Y, Wheeler C, Huffman AK, Chapman C, Dobrunz LE, Levey A, Roth KA, Wilson JA, Wilson SM. Transgenic Rescue ofataxiaMice with Neuronal-Specific Expression of Ubiquitin-Specific Protease 14. The Journal of Neuroscience. Society for Neuroscience; 2006 Nov 1;26(44):11423–11431.

Published In

The Journal of Neuroscience

DOI

EISSN

1529-2401

ISSN

0270-6474

Publication Date

November 1, 2006

Volume

26

Issue

44

Start / End Page

11423 / 11431

Publisher

Society for Neuroscience

Related Subject Headings

  • Neurology & Neurosurgery
  • 17 Psychology and Cognitive Sciences
  • 11 Medical and Health Sciences