Developmental regulation of a cloned adult β-globin gene in transgenic mice
Developmental regulation of a cloned adult β-globin gene in transgenic mice
复制标题
转基因小鼠中克隆的成年β-珠蛋白基因的发育调控
作者：
J. Magram;K. Chada;F. Costantini
在哺乳动物发育的不同阶段，不同的胚胎、胎儿和成年血红蛋白在红系细胞中合成，这一过程被称为血红蛋白转换。控制血红蛋白转换的细胞和分子机制已经被深入研究，但仍然知之甚少。为了研究珠蛋白基因表达的发育规律，我们培育了转基因MIE2-6，其中克隆的珠蛋白基因存在于红系细胞的整个发育过程中。最近，我们报道了在几个携带人/鼠混合β-珠蛋白基因的转基因系中，成年小鼠以正确的组织特异性方式表达了该基因。这一发现提出了一个问题，即外源珠蛋白基因是否也可能受到适当的阶段特定调控。与内源性成体β-珠蛋白基因一样，杂合β-珠蛋白基因在卵黄囊来源的胚胎红系细胞中不表达，并首次在胎肝红系细胞中表达。我们的结果表明，与成人β珠蛋白基因紧密连锁的顺式作用调控元件可以赋予特定阶段的表达模式。他们还表明，小鼠的胚胎和成年β-珠蛋白基因被存在于胚胎、胎儿和成年红系细胞中的不同反式调节因子激活(或抑制)。
At different stages of mammalian development, distinct embryonic, fetal and adult haemoglobins are synthesized in erythroid cells, a process termed haemoglobin switching. The cellular and molecular mechanisms controlling haemoglobin switching have been intensively studied, but remain poorly understood1. To study the developmental regulation of globin gene expression, we have produced transgenic mice2–6 in which cloned globin genes are present in erythroid cells throughout development. Recently, we reported that adult mice in several transgenic lines carrying a hybrid mouse/human adult β-globin gene, expressed the gene in a correct tissue-specific manner7. This finding raised the question of whether an exogenous globin gene could also be subject to appropriate stage-specific regulation. We report here that the hybrid β-globin gene, like the endogenous adult β-globin genes, is inactive in yolk sac-derived embryonic erythroid cells and is expressed for the first time in fetal liver erythroid cells. Our results indicate that a stage-specific pattern of expression can be conferred by cis- acting regulatory elements closely linked to an adult β-globin gene. They also suggest that the embryonic and adult β-globin genes in the mouse are activated (or repressed) by distinct trans-acting regulatory factors present in embryonic, fetal and adult erythroid cell.
外源人珠蛋白基因在人红白血病（K562）细胞中的稳定转移和表达。
DOI：
10.1073/pnas.81.17.5315
发表时间：
1984
影响因子：
11.1
作者：
Young,K;Donovan-Peluso,M;Bloom,K;Allan,M;Paul,J;Bank,A
通讯作者：
Bank,A
小鼠 beta h1 基因编码胚胎血红蛋白的 z 链。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Farace,MG;Brown,BA;Raschellà,G;Alexander,J;Gambari,R;Fantoni,A;Hardies,SC;Hutchison3rd,CA;Edgell,MH
通讯作者：
Edgell,MH
DOI：
10.1073/pnas.77.12.7380
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GORDON, JW;SCANGOS, GA;RUDDLE, FH
通讯作者：
RUDDLE, FH