Stroud Dina Myers, Darrow Bruce J, Kim Sang Do, Zhang Jie, Jongbloed Monique R M, Rentschler Stacey, Moskowitz Ivan P G, Seidman Jonathan, Fishman Glenn I
Genesis. 2007 Feb;45(2):76-82. doi: 10.1002/dvg.20267.
The cardiac conduction system (CCS)-lacZ insertional mouse mutant strain genetically labels the developing and mature CCS. This pattern of expression is presumed to reflect the site of transgene integration rather than regulatory elements within the transgene proper. We sought to characterize the genomic structure of the integration locus and identify nearby gene(s) that might potentially confer the observed CCS-specific transcription. We found rearrangement of chromosome 7 between regions D1 and E1 with altered transcription of multiple genes in the D1 region. Several lines of evidence suggested that regulatory elements from at least one gene, Slco3A1, influenced CCS-restricted reporter gene expression. In embryonic hearts, Slco3A1 was expressed in a spatial pattern similar to the CCS-lacZ transgene and was similarly neuregulin-responsive. At later stages, however, expression patterns of the transgene and Slco3A1 diverged, suggesting that the Slco3A1 locus may be necessary, but not sufficient to confer CCS-specific transgene expression in the CCS-lacZ line.
心脏传导系统（CCS）-lacZ插入型小鼠突变株可对发育中和成熟的CCS进行基因标记。这种表达模式被认为反映的是转基因整合位点，而非转基因本身的调控元件。我们试图表征整合位点的基因组结构，并鉴定可能潜在赋予所观察到的CCS特异性转录的附近基因。我们发现7号染色体在D1和E1区域之间发生了重排，且D1区域中多个基因的转录发生了改变。几条证据表明，至少一个基因Slco3A1的调控元件影响了CCS限制性报告基因的表达。在胚胎心脏中，Slco3A1以与CCS-lacZ转基因相似的空间模式表达，并且对神经调节蛋白的反应也相似。然而，在后期，转基因和Slco3A1的表达模式出现了分歧，这表明Slco3A1基因座可能是CCS-lacZ系中赋予CCS特异性转基因表达所必需的，但并不充分。
