Elastase I promoter directs expression of human growth hormone and SV40 T antigen genes to pancreatic acinar cells in transgenic mice.
Elastase I promoter directs expression of human growth hormone and SV40 T antigen genes to pancreatic acinar cells in transgenic mice.
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弹性蛋白酶 I 启动子指导转基因小鼠的胰腺腺泡细胞表达人类生长激素和 SV40 T 抗原基因。
DOI：
10.1101/sqb.1985.050.01.050
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Brinster,RL
中科院分区：
文献类型：
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作者：
Ornitz,DM;Palmiter,RD;Messing,A;Hammer,RE;Pinkert,CA;Brinster,RL
外分泌胰腺与前肠的内皮细胞不同，其功能是合成和储存释放到肠道中的消化酶。胰腺还含有可能是外胚层起源的内分泌细胞，其产生代谢调节激素，包括胰岛素、胰高血糖素和生长抑素。在小鼠发育期间，胰腺腺泡细胞可在约第10天被检测到，并且在第11天和第14天之间开始合成低水平的消化酶。出生前不久，这些酶的水平急剧增加，在出生后的前几周内达到成人水平（Rutter等人，1972年）。胰腺丝氨酸蛋白酶基因的表达在腺泡细胞中比在任何其他细胞类型中高几个数量级（Swift等，1984 a）。因为这些消化酶在不适当的组织中的表达可能对生物体有害，所以可能存在强烈的选择压力来维持这种非常精确的细胞特异性表达。为了了解这个消化酶家族的调控机制，我们开始研究大鼠弹性蛋白酶I基因的调控。该基因是仅在胰腺腺泡细胞中表达的至少九种丝氨酸蛋白酶基因之一。细胞特异性基因表达的调节正在通过将各种基因引入保持分化表型的组织培养细胞或通过产生携带这些基因的转基因小鼠来研究。虽然顺式作用，细胞特异性元件已被确定为各种基因的DNA介导转染到细胞中（Banerji等，1983; Chao等，1983;吉利斯等，1983; Kondoh等，1983;斯塔福德和Queen，1983;步行者等人，1983年），转基因小鼠具有明显的优势，即在整个正常发育过程中，可以在每种可能的细胞类型中测定发育调节基因。老鼠.此外，在转基因小鼠中观察到许多基因的正常表达水平，而在组织培养中，分化基因的表达水平通常非常低。在转基因小鼠中，免疫球蛋白重链和轻链基因（Brinster等1983; Grosschedl等1984; Storb等1984; Rusconi和科勒1985）、弹性蛋白酶I基因（Swift等1984 a;
The exocrine pancreas, which differentiates from the endothelial cells of the foregut, functions to synthesize and store digestive enzymes that are released into the intestinal tract. The pancreas also contains endocrine cells probably of ectodermal origin, which produce metabolic regulatory hormones, including insulin, glucagon, and somatostatin. During mouse development the pancreatic acinar cells can be detected by about day 10 and begin to synthesize low levels of digestive enzymes between days 11 and 14. Shortly before birth the levels of these enzymes increase dramatically and adult levels are attained within the first several weeks of life (Rutter et al. 1972). Expression of pancreatic serine protease genes is several orders of magnitude higher in the acinar cell than in any other cell type (Swift et al. 1984a). Because expression of these digestive enzymes in inappropriate tissues could be deleterious to an organism, there may be strong selective pressure to maintain this very precise cell-specific expression. To gain an understanding of the regulatory mechanisms governing this family of digestive enzymes, we have begun studying the regulation of the rat elastase I gene. This gene is one of at least nine serine protease genes expressed exclusively in pancreatic acinar cells. Regulation of cell-specific gene expression is being studied by introducing various genes into tissue culture cells that maintain a differentiated phenotype or by producing transgenic mice carrying these genes. Although cis-acting, cell-specific elements have been identified for a variety of genes by DNA-mediated transfection into cells (Banerji et al. 1983; Chao et al. 1983; Gillies et al. 1983; Kondoh et al. 1983; Stafford and Queen 1983; Walker et al. 1983), transgenic mice have the distinct advantage that developmentally regulated genes can be assayed in every possible cell type throughout the normal development of the mouse. Furthermore, normal levels of expression are observed for many genes in transgenic mice, whereas in tissue culture the level of expression of differentiated genes is often very low. In transgenic mice, tissue-specific expression has been demonstrated for immunoglobulin heavy-and light-chain genes (Brinster et al. 1983; Grosschedl et al. 1984; Storb et al. 1984; Rusconi and Kohler 1985), the elastase I gene (Swift et al. 1984a;