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E-GEOD-29909 - Modeling OPMD in myotube cultures reveals reduced accumulation of soluble mutant PABPN1 protein

Released on 31 August 2011, last updated on 14 September 2011
Mus musculus
Samples (10)
Array (1)
Protocols (8)
Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease caused by an alanine tract expansion mutation in Poly(A)-binding protein nuclear 1 (expPABPN1). To model OPMD in a myogenic and physiological context, we generated mouse myoblast cell clones stably expressing either human wild type (WT) or expPABPN1 at low levels. The transgene expression is induced upon myotube differentiation and results in formation of insoluble nuclear PABPN1 aggregates that are similar to the in vivo aggregates. Quantitative analysis of PABPN1 protein in myotube cultures revealed that expPABPN1 accumulation and aggregation is greater than that of the WT protein. In a comparative study we found that aggregation of expPABPN1 is more affected by inhibition of proteasome activity, as compared with the WT PABPN1 aggregation. Consistent with this, in myotubes cultures expressing expPABPN1 deregulation of the proteasome was identified as the most significantly deregulated pathway. Differences in the accumulation of soluble WT and expPABPN1 were consistent with differences in ubiquitination and protein turnover. This study indicates, for the first time, that in myotubes the ratio of soluble to insoluble expPABPN1 is significantly lower compared to that of the WT protein. We suggest that this difference can contribute to muscle weakness in OPMD. Clones on IM2 mouse myotubes that stably express Ala10-PABPN1-FLAG (WTA, WTD) or Ala17-PABPN1-FLAG (D7E). The transgene expression level in D7E and WTA are similar. WTA and WTD reflects differences in expression levels. RNA was extracted from myotubes of WTA, WTD and D7E in triplicates. cDNA synthesis and lebeling was preformed with the Illumina cDNA labeling kit.
Experiment type
transcription profiling by array 
Seyed Yahya Anvar <>, Andrea Venema, Erik van der Wal, Hellen Buijze, Kirsten R Straasheijm, Michael Antoniou, Rinse Klooster, Samantha Routledge, Silvere M van der Maarel, Vered Raz
Investigation descriptionE-GEOD-29909.idf.txt
Sample and data relationshipE-GEOD-29909.sdrf.txt
Processed data (1)
Array designA-MEXP-1175.adf.txt