RGD Reference Report - Pathophysiological defects and transcriptional profiling in the RBM20-/- rat model. - Rat Genome Database

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Pathophysiological defects and transcriptional profiling in the RBM20-/- rat model.

Authors: Guo, Wei  Pleitner, Jonathan M  Saupe, Kurt W  Greaser, Marion L 
Citation: Guo W, etal., PLoS One. 2013 Dec 19;8(12):e84281. doi: 10.1371/journal.pone.0084281. eCollection 2013.
RGD ID: 126925234
Pubmed: PMID:24367651   (View Abstract at PubMed)
PMCID: PMC3868568   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0084281   (Journal Full-text)

Our recent study indicated that RNA binding motif 20 (Rbm20) alters splicing of titin and other genes. The current goals were to understand how the Rbm20(-/-) rat is related to physiological, structural, and molecular changes leading to heart failure. We quantitatively and qualitatively compared the expression of titin isoforms between Rbm20(-/-) and wild type rats by real time RT-PCR and SDS agarose electrophoresis. Isoform changes were linked to alterations in transcription as opposed to translation of titin messages. Reduced time to exhaustion with running in knockout rats also suggested a lower maximal cardiac output or decreased skeletal muscle performance. Electron microscopic observations of the left ventricle from knockout animals showed abnormal myofibril arrangement, Z line streaming, and lipofuscin deposits. Mutant skeletal muscle ultrastructure appeared normal. The results suggest that splicing alterations in Rbm20(-/-) rats resulted in pathogenic changes in physiology and cardiac ultrastructure. Secondary changes were observed in message levels for many genes whose splicing was not directly affected. Gene and protein expression data indicated the activation of pathophysiological and muscle stress-activated pathways. These data provide new insights on Rbm20 function and how its malfunction leads to cardiomyopathy.

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Rbm20  (RNA binding motif protein 20)
Rbm20m1Mlgw  (RNA binding motif protein 20; mutation 1, Marion Greaser)

(SDxF344)F1-Rbm20m1Mlgw  (NA)

Additional Information