Paleyanda R K, Zhang D W, Hennighausen L, McKnight R A, Lubon H
Holland Laboratory, American Red Cross, Rockville, MD 20855.
Transgenic Res. 1994 Nov;3(6):335-43. doi: 10.1007/BF01976765.
A 4.1 kb mouse whey acidic protein (mWAP) promoter was cloned from a C57BL/6 cosmid library. The tissue-specific and developmental pattern of expression of a hybrid gene comprised of the mWAP promoter fragment and the human protein C (HPC) gene was analysed in transgenic mice. The corresponding RNA was detected mainly in the mammary gland, with 'leakage' of expression in the salivary gland and kidney. The developmental pattern of transgene expression differed from that of the endogenous WAP gene. In particular, recombinant HPC (rHPC) transcripts were detected earlier in pregnancy than WAP RNA, with no significant increase during lactation. This indicates that regulatory elements responsible for developmental regulation are located outside the 4.1 kb mWAP gene promoter fragment, or if present, may be subject to position effects. Precocious expression of the transgene did not compromise the health or nursing abilities of transgenic females. Expression of rHPC affected the appearance of the mammary alveoli and alveolar epithelial cells in lactating transgenic mice. The alveoli were less distended and alveolar epithelial cells appeared cuboidal with centrally positioned nuclei. We suggest that the inefficient intracellular processing of rHPC can alter the histological appearance of alveolar epithelial cells in the transgenic mammary gland.
从小鼠C57BL/6黏粒文库中克隆出一个4.1 kb的小鼠乳清酸性蛋白（mWAP）启动子。在转基因小鼠中分析了由mWAP启动子片段和人蛋白C（HPC）基因组成的杂交基因的组织特异性和发育表达模式。相应的RNA主要在乳腺中检测到，在唾液腺和肾脏中有表达“渗漏”。转基因表达的发育模式与内源性WAP基因不同。特别是，重组HPC（rHPC）转录本在妊娠早期比WAP RNA更早被检测到，在哺乳期没有显著增加。这表明负责发育调控的调控元件位于4.1 kb mWAP基因启动子片段之外，或者即使存在，也可能受到位置效应的影响。转基因的早熟表达并未损害转基因雌性小鼠的健康或哺乳能力。rHPC的表达影响了哺乳期转基因小鼠乳腺腺泡和腺泡上皮细胞的外观。腺泡扩张程度较小，腺泡上皮细胞呈立方形，细胞核位于中央。我们认为rHPC在细胞内加工效率低下会改变转基因乳腺中腺泡上皮细胞的组织学外观。
