DWARF MICE PRODUCED BY GENETIC ABLATION OF GROWTH HORMONE-EXPRESSING CELLS
DWARF MICE PRODUCED BY GENETIC ABLATION OF GROWTH HORMONE-EXPRESSING CELLS
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DOI：
10.1101/gad.2.4.453
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发表时间：
1988-04-01
影响因子：
10.5
通讯作者：
BRINSTER, RL
中科院分区：
文献类型：
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作者：
BEHRINGER, RR;MATHEWS, LS;BRINSTER, RL
将大鼠生长激素（GH）基因5英寸处310 bp的基因与人生长激素结构基因融合，在转基因小鼠中产生了生长特异性表达。人类生长激素转录本仅在这些小鼠的垂体中检测到，免疫细胞化学分析显示这种表达仅限于表达GH的细胞类型。大鼠GH 5”序列被用来指导白喉毒素在转基因小鼠GH表达细胞中的表达。建立了一种缺乏可检测到的循环GH水平的小鼠系。这种缺陷导致了侏儒症；转基因动物只能长到非转基因动物的一半大小。转基因垂体的生长激素免疫染色显示，几乎所有的生长色素都不存在。产生催乳素（PRL）的乳异构体，被认为与生长异构体有共同的细胞起源，数量也减少了。提出了GH-和prl合成细胞之间的线性关系模型。
Fusion of the 310 bp located 5'' of the rat growth hormone (GH) gene to the human GH structural gene resulted in somatotrope-specific expression in transgenic mice. Human GH transcripts were detected only in pituitaries of these mice, and immunocytochemical analyses revealed that this expression was limited to GH-expressing cell types. The rat GH 5'' sequences were than used to direct the expression of diphtheria toxin to the GH-expressing cells of transgenic mice. A line of mice was established which lacks detectable levels of circulating GH. This deficiency resulted in dwarfism; transgenic animals grew only to half the size of nontransgenic littermates. Nearly all somatotropes were absent, as shown by GH immunostaining in the transgenic pituitaries. Prolactin (PRL)-producing lactotropes, thought to share a common cellular origin with somatotropes, were also reduced in numbers. A model for the lineal relationships between GH- and PRL-synthesizing cells is proposed.