WIDESPREAD EXPRESSION OF HUMAN ALPHA-1-ANTITRYPSIN IN TRANSGENIC MICE REVEALED BY INSITU HYBRIDIZATION
WIDESPREAD EXPRESSION OF HUMAN ALPHA-1-ANTITRYPSIN IN TRANSGENIC MICE REVEALED BY INSITU HYBRIDIZATION
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DOI：
10.1101/gad.3.1.16
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发表时间：
1989-01-01
影响因子：
10.5
通讯作者：
LOVELLBADGE, RH
中科院分区：
文献类型：
--
作者：
KOOPMAN, P;POVEY, S;LOVELLBADGE, RH
原位杂交是鉴定基因表达位点的有力手段。我们使用该技术来检测携带人α 1-抗胰蛋白酶（α 1AT）基因和广泛的5“-和3”-侧翼序列的转基因小鼠中该基因转录的空间和发育控制。除了在卵黄囊和肝脏中的表达外，在妊娠后14.5天（dpc），在转基因胎儿的肠、胃、胰腺、鼻上皮、咽、支气管、脊神经节和骨化软骨中检测到人α 1AT RNA。在转基因成人中，胰腺中不再发现表达，但在肾脏和唾液腺中发现了表达。在每个组织中，表达仅限于特定的细胞群。发现这种α 1AT表达模式与在几种胎儿和成人组织中所见的相关。这些结果表明α 1AT在人类生理学和发育中的作用比以前怀疑的更广泛，并且它们证明了这种方法在描绘人类蛋白质的生理学作用中的潜在价值。内源性α 1AT基因在小鼠中的表达局限于有限的但重叠的一组组织，表明调节人和小鼠基因表达的顺式作用DNA序列与小鼠细胞中存在的转录因子不同地相互作用。
In situ hybridization is a powerful means of identifying sites of gene expression. We used this technique to examine the spatial and developmental control of transcription of the human .alpha.1-antitrypsin (.alpha.1AT) gene in transgenic mice carrying this gene and extensive 5''- and 3''-flanking sequences. In addition to expression in yolk sac and liver, human .alpha.1AT RNA was detected in gut, stomach, pancreas, nasal epithelium, pharynx, bronchi, spinal ganglia, and ossifying cartilage of transgenic fetuses at 14.5 days post coitum (dpc). In transgenic adults, expression was no longer found in the pancreas but was found in the kidney and salivary gland. In each tissue, expression was confined to a specific cell population. This pattern of .alpha.1AT expression was found to correlate with that seen in several fetal and adult human tissues. These results suggest a wider role of .alpha.1AT in human physiology and development than previously suspected, and they demonstrated the potential value of this approach in delineating the physiological role of human proteins. Expression of the endogenous .alpha.1AT gene in mice was confined to a limited, but overlapping, set of tissues, suggesting that the cis-acting DNA sequences that regulate the expression of the human and mouse genes interact differently with transcription factors present in mouse cells.