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| Status |
Public on Feb 23, 2012 |
| Title |
Expression analysis of pre-phenotype dt27J mouse dorsal root ganglia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Loss of function of dystonin cytoskeletal linker proteins causes neurodegeneration in the sensory ataxia, dystonia musculorum (dt). While much investigation has focused on understanding dt pathology, divergent functions of dystonin isoforms are still unknown. Here, we highlight a novel function of the dystonin-a2 isoform in mediating microtubule (MT) stability, golgi organization and flux through the secretory pathway. Using dystonin-null mice combined with isoform-specific loss of function analysis, we find dystonin-a2 is bound to MAP1B in the area surrounding the centrosome, where it maintains MT acetylation. In dt, the absence of the MAP1B-dystonin-A2 interaction results in a loss of MAP1B perinuclear localization, leading to MT deacetylation and instability. Deacetylated MTs lead to golgi fragmentation and prevent anterograde trafficking of motor proteins. Maintenance of MT acetylation through TSA administration or MAP1B overexperssion in vitro, mitigates the observed defect. These aberrations are apparent in pre-phenotype dorsal root ganglia (DRG) and primary sensory neurons, suggesting they are causal in the dt disorder.
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| Overall design |
P4 dorsal root ganglia (DRG) tissue from 3 WT and 3 dt27J animals from 2 separate litters was subjected to RNA extraction and analyzed.
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| Contributor(s) |
Ryan SD, Chu A, Blais A, Kothary R |
| Citation(s) |
22412020 |
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| Submission date |
Jul 26, 2011 |
| Last update date |
Jan 12, 2017 |
| Contact name |
Scott D Ryan |
| Organization name |
Ottawa Hospital Research Institute
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| Department |
Regenerative Medicine
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| Lab |
Kothary Lab
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| Street address |
501 Smyth Rd
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| City |
Ottawa |
| State/province |
ON |
| ZIP/Postal code |
K1H 8L6 |
| Country |
Canada |
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| Platforms (1) |
| GPL7202 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA146157 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30960_RAW.tar |
9.2 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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