Behringer R R, Mathews L S, Palmiter R D, Brinster R L
Laboratory of Reproductive Physiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104.
Genes Dev. 1988 Apr;2(4):453-61. doi: 10.1101/gad.2.4.453.
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 then 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.
将大鼠生长激素（GH）基因5'端的310 bp片段与人生长激素结构基因融合，导致转基因小鼠中促生长激素细胞特异性表达。仅在这些小鼠的垂体中检测到人生长激素转录本，免疫细胞化学分析表明这种表达仅限于表达生长激素的细胞类型。然后利用大鼠生长激素5'端序列将白喉毒素的表达导向转基因小鼠的生长激素表达细胞。建立了一系列循环生长激素水平检测不到的小鼠品系。这种缺陷导致侏儒症；转基因动物的生长仅为非转基因同窝仔鼠的一半大小。转基因垂体中的生长激素免疫染色显示，几乎所有促生长激素细胞都不存在。与促生长激素细胞具有共同细胞起源的分泌催乳素（PRL）的促乳素细胞数量也减少。提出了生长激素和催乳素合成细胞之间线性关系的模型。
