TISSUE-SPECIFIC, HIGH-LEVEL EXPRESSION OF THE RAT WHEY ACIDIC PROTEIN GENE IN TRANSGENIC MICE
TISSUE-SPECIFIC, HIGH-LEVEL EXPRESSION OF THE RAT WHEY ACIDIC PROTEIN GENE IN TRANSGENIC MICE
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DOI：
10.1093/nar/18.10.2977
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发表时间：
1990-05-25
影响因子：
14.9
通讯作者：
ROSEN, JM
中科院分区：
文献类型：
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作者：
BAYNA, EM;ROSEN, JM
基因内和 3'' 侧翼序列在控制牛奶乳清酸性蛋白 (WAP) 的时间、激素和组织特异性表达中的重要性已在转基因小鼠中得到证实。产生了携带 4.3 kb 基因组克隆的小鼠品系，该克隆包含完整的大鼠 WAP 基因减去第一个内含子的 200 bp，以及 0.949 kb 的 5'' 和 1.4 kb 的 3'' 侧翼 DNA。在所分析的 9 个独立小鼠系中，有 8 个小鼠检测到 WAP 转基因表达水平为内源基因的 1% 至 95%（平均为 27%）。转基因优先在乳腺中表达。尽管在怀孕和哺乳期间受到发育调节，但 WAP 转基因表达的时间模式与内源基因不同。在怀孕 7 天时检测到转基因表达的提前增加，比内源性小鼠 WAP mRNA 中观察到的主要增加早了几天。大鼠 WAP 转基因被翻译并分泌到转基因小鼠的乳汁中，其水平与内源性小鼠 WAP 相当。这是第一个关于在分离细胞培养物和转染细胞中受到负调控但在转基因小鼠的正确多细胞环境中有效表达的基因的报告。
The importance of intragenic and 3'' flanking sequences in the control of the temporal, hormonal and tissue-specific expression of milk whey acidic protein (WAP) has been demonstrated in transgenic mice. Mouse lines carrying a 4.3 kb genomic clone containing the entire rat WAP gene minus 200 bp of the first intron with 0.949 kb of 5'' and 1.4 kb of 3'' flanking DNA were generated. In eight of nine independent lines of mice analyzed, WAP transgene expression was detected at levels ranging from 1% to 95% (average, 27%) of the endogenous gene. The transgene was expressed preferentially in the mammary gland. Although developmentally regulated during pregnancy and lactation, the temporal pattern of WAP transgene expression differed from the endogenous gene. A precocious increase in expression of the transgene was detected at 7 days of pregnancy, several days earlier in pregnancy than the major increase observed in endogenous mouse WAP mRNA. The rat WAP transgene was translated and secreted into the milk of transgenic mice at levels comparable to the endogenous mouse WAP. This is the first report of a gene that is negatively regulated in dissociated cell cultures as well as in transfected cells, yet is expressed efficiently in the correct multicellular environment of the transgenic mouse.