Gardner D G, Camargo M J, Behringer R R, Brinster R L, Baxter J D, Atlas S A, Laragh J H, Deschepper C F
Department of Medicine, University of California, San Francisco 94143.
Am J Physiol. 1992 Apr;262(4 Pt 1):E524-31. doi: 10.1152/ajpendo.1992.262.4.E524.
Transgenic mice harboring a chimeric gene linking mouse protamine 1 5'-flanking sequence to the coding sequence of the simian virus 40 T-antigen develop spontaneous rhabdomyosarcomas of the right atria. The presence of the tumors is accompanied by dramatic elevations in plasma atrial natriuretic peptide (ANP) immunoreactivity (1,698 +/- 993 vs. 60 +/- 18 fmol/ml for controls) and hematocrit (56 +/- 8 vs. 51 +/- 2 for controls). The immunoreactive ANP (irANP) present in the tumors is similar in size to irANP found in normal mouse atria. ANP mRNA transcripts present in the tumors also appear to be very similar in overall size and 5'-termini to those produced in normal cardiac tissue. Microscopically, the tumors are composed of a disorganized array of densely packed abnormal-appearing cells. Immunocytochemistry and in situ hybridization analysis reveal considerable heterogeneity in ANP gene expression. ANP peptide and mRNA are detectable throughout the parenchyma of the tumors, but absolute levels of expression vary widely among different cells in the population. These tumors represent a potentially valuable model for the study of inappropriate ANP secretion and may provide a tissue source for the development of an ANP-producing atrial cell line.
携带将小鼠鱼精蛋白1的5'侧翼序列与猿猴病毒40 T抗原编码序列连接起来的嵌合基因的转基因小鼠会自发发生右心房横纹肌肉瘤。肿瘤的出现伴随着血浆心钠素（ANP）免疫反应性的显著升高（对照组为60±18 fmol/ml，肿瘤小鼠为1,698±993 fmol/ml）以及血细胞比容的升高（对照组为51±2，肿瘤小鼠为56±8）。肿瘤中存在的免疫反应性心钠素（irANP）在大小上与正常小鼠心房中发现的irANP相似。肿瘤中存在的心钠素mRNA转录本在总体大小和5'末端上似乎也与正常心脏组织中产生的转录本非常相似。在显微镜下，肿瘤由排列紊乱的密集堆积的异常细胞组成。免疫细胞化学和原位杂交分析显示心钠素基因表达存在相当大的异质性。在肿瘤实质中可检测到心钠素肽和mRNA，但不同细胞群体中的绝对表达水平差异很大。这些肿瘤代表了一个研究不适当的心钠素分泌的潜在有价值的模型，并可能为开发产生心钠素的心房细胞系提供组织来源。
