Gene expression patterns in transgenic mouse models of hypertrophic cardiomyopathy caused by mutations in myosin regulatory light chain

Wenrui Huang, Katarzyna Kazmierczak, Zhiqun Zhou, Vanessa Aguiar-Pulido, Giri Narasimhan, Danuta Szczesna-Cordary

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Using microarray and bioinformatics, we examined the gene expression profiles in transgenic mouse hearts expressing mutations in the myosin regulatory light chain shown to cause hypertrophic cardiomyopathy (HCM). We focused on two malignant RLC-mutations, Arginine 58→Glutamine (R58Q) and Aspartic Acid 166 → Valine (D166V), and one benign, Lysine 104 → Glutamic Acid (K104E)-mutation. Datasets of differentially expressed genes for each of three mutants were compared to those observed in wild-type (WT) hearts. The changes in the mutant vs. WT samples were shown as fold-change (FC), with stringency FC ≥ 2. Based on the gene profiles, we have identified the major signaling pathways that underlie the R58Q-, D166V- and K104E-HCM phenotypes. The correlations between different genotypes were also studied using network-based algorithms. Genes with strong correlations were clustered into one group and the central gene networks were identified for each HCM mutant. The overall gene expression patterns in all mutants were distinct from the WT profiles. Both malignant mutations shared certain classes of genes that were up or downregulated, but most similarities were noted between D166V and K104E mice, with R58Q hearts showing a distinct gene expression pattern. Our data suggest that all three HCM mice lead to cardiomyopathy in a mutation-specific manner and thus develop HCM through diverse mechanisms.

Original languageEnglish (US)
JournalArchives of Biochemistry and Biophysics
DOIs
StateAccepted/In press - Nov 1 2015

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Keywords

  • Differential gene expression
  • Microarray
  • Network/centrality analysis
  • Pathological hypertrophy
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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