Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart

Dumitru A. Iacobas, Sanda Iacobas, W. E I Li, Georg Zoidl, Rolf Dermietzel, David C. Spray

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

We have used mouse 27k cDNA arrays to compare gene expression patterns in four sets of three hearts each of neonatal wild types and four sets of three hearts each of littermates lacking the major cardiac gap junction protein, connexin43 (Cx43). Each individual set of hearts was hybridized against aliquots of an RNA standard prepared from selected mouse tissues, allowing calculation of variability and coordination of gene expression among the samples from both genotypes. Overall variance of gene expression was found to be markedly higher in wild-type hearts than in those from Cx43 null littermates. Expression levels of 586 of 5,613 adequately quantifiable distinct genes with known protein products were statistically altered in the Cx43 null hearts, 38 upregulated and 548 downregulated compared with wild types. Downregulation was confirmed for seven tested genes by quantitative RT-PCR. Functions of proteins encoded by the altered genes encompassed all functional categories, with largest percent changes in genes involved in intracellular transport and transcription factors. Among the downregulated genes in the Cx43 null hearts were those related to neuronal and glial function, suggesting that cardiac innervation might be compromised as a consequence of Cx43 deletion. This was supported by immunodetection of sympathetic innervation, using antibodies to the synaptic vesicle protein synaptophysin and to the adrenergic nerve terminal marker tyrosine hydroxylase. These findings reinforce the proposal that the cardiac abnormality in Cx43 null animals may be contributed by altered innervation and indicate that Cx43 deletion has consequences in addition to reduced intercellular communication.

Original languageEnglish (US)
Pages (from-to)211-223
Number of pages13
JournalPhysiological Genomics
Volume20
DOIs
StatePublished - Apr 2005

Fingerprint

Connexin 43
Genes
Down-Regulation
Gene Expression
Synaptophysin
Proteins
Connexins
Synaptic Vesicles
Tyrosine 3-Monooxygenase
Oligonucleotide Array Sequence Analysis
Neuroglia
Adrenergic Agents
Transcription Factors
Genotype
RNA
Polymerase Chain Reaction
Antibodies

Keywords

  • Cardiac innervation
  • cDNA array
  • Expression coordination
  • Transcription control

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart. / Iacobas, Dumitru A.; Iacobas, Sanda; Li, W. E I; Zoidl, Georg; Dermietzel, Rolf; Spray, David C.

In: Physiological Genomics, Vol. 20, 04.2005, p. 211-223.

Research output: Contribution to journalArticle

Iacobas, Dumitru A. ; Iacobas, Sanda ; Li, W. E I ; Zoidl, Georg ; Dermietzel, Rolf ; Spray, David C. / Genes controlling multiple functional pathways are transcriptionally regulated in connexin43 null mouse heart. In: Physiological Genomics. 2005 ; Vol. 20. pp. 211-223.
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