Transcriptomic characterization of four classes of cell-cell/cell-matrix genes in brains and hearts of wild type and connexin43 null mice.
We have used a highly quantifiable cDNA microarray method to determine the stabilities and expression levels within gene families involved in cell-cell and cell-matrix interactions in neonatal mouse brain and heart. In addition, we have characterized the extent to which deletion of the gap junction protein connexin43 (Cx43) affects these characteristics. Our observations for individual genes revealed a range of differences and variabilities in transcription level among family members; calculation of the genomic patholog (a global measure of gene expression alteration) indicates that these cell interaction genes contribute disproportionately to the overall phenotype. We found significant transcriptomic differences between brain and heart, that deletion of Cx43 considerably decreased gene expression variability and that the average contribution to the pathology of the genes whose encoded proteins are involved in cell-cell or cell-matrix interaction in the Cx43-null mice was about twenty times higher than that of other genes. These findings indicate that gap junction gene expression influences the expression of other genes involved in intercellular and cell-substrate interaction and that expression of these genes is under strong regulatory pressure in the Cx43-null mouse, presumably representing a compensatory response to Cx43 deletion.
Rose F. Kennedy Center, Albert Einstein College of Medicine, 1410 Pelham Parkway South, New York, NY 10461, USA. diacobas@aecom.yu.ed
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Iacobaş
Marcia
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Urban
Sanda
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Iacobaş
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Spray
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002450:Cell Communication / Q000235:genetics*; D021982:Cell-Matrix Junctions / Q000187:drug effects*; D018031:Connexin 43 / Q000172:deficiency*; D015870:Gene Expression; D006321:Heart / Q000503:physiopathology*; D016023:Integrins / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018031:Connexin 43; D016023:Integrins; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases