Iacobaş D A, Urban Marcia, Iacobaş Sanda, Spray D C
Rose F. Kennedy Center, Albert Einstein College of Medicine, 1410 Pelham Parkway South, New York, NY 10461, USA.
Rom J Physiol. 2002;39-40:91-116.
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.
我们采用了一种高度可量化的cDNA微阵列方法,来确定新生小鼠脑和心脏中参与细胞间和细胞与基质相互作用的基因家族内的稳定性和表达水平。此外,我们还描述了缝隙连接蛋白连接蛋白43(Cx43)的缺失对这些特征的影响程度。我们对单个基因的观察揭示了家族成员之间转录水平的一系列差异和变异性;基因组病理学计算(基因表达改变的整体测量)表明,这些细胞相互作用基因对整体表型的贡献不成比例。我们发现脑和心脏之间存在显著的转录组差异,Cx43的缺失显著降低了基因表达变异性,并且在Cx43基因敲除小鼠中,其编码蛋白参与细胞间或细胞与基质相互作用的基因对病理学的平均贡献比其他基因高约20倍。这些发现表明,缝隙连接基因表达影响参与细胞间和细胞与底物相互作用的其他基因的表达,并且在Cx43基因敲除小鼠中,这些基因的表达受到强烈的调控压力,推测这代表了对Cx43缺失的一种补偿反应。