Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes.
Transgenic rats reveal functional conservation of regulatory controls between the Fugu isotocin and rat oxytocin genes.
复制标题
DOI：
10.1073/pnas.94.23.12462
复制
发表时间：
1997-11
影响因子：
11.1
通讯作者：
B. Venkatesh;S. Si-Hoe;D. Murphy;S. Brenner
中科院分区：
文献类型：
--
作者：
B. Venkatesh;S. Si-Hoe;D. Murphy;S. Brenner
我们询问是否可以使用比较基因组分析和大鼠转基因来识别编码下丘脑神经肽催产素（OT）和加压素的基因座中的功能调节域。异产素 (IT) 和加压素 (VT) 是这些基因的硬骨鱼同源物。跨越 Fugu IT-VT 基因座的 46 kb 连续片段已被测序，并发现了 9 个推定基因。与在哺乳动物基因组中以尾对尾方向紧密相连的 OT 和加压素基因不同，Fugu IT 和 VT 基因头对尾相连，并由五个基因分开。当将含有 Fugu IT-VT 基因座的粘粒引入大鼠基因组时，我们发现 Fugu IT 基因在大鼠下丘脑催产素能神经元中特异性表达，并模仿内源性 OT 基因对渗透刺激的反应。这些数据表明，介导OT和IT基因的细胞特异性和生理调节的顺式作用元件和反式作用因子在哺乳动物和鱼类之间是保守的。河豚基因组分析和哺乳动物转基因的结合是鉴定和分析保守脊椎动物调控元件的强大工具。
We have asked whether comparative genome analysis and rat transgenesis can be used to identify functional regulatory domains in the gene locus encoding the hypothalamic neuropeptides oxytocin (OT) and vasopressin. Isotocin (IT) and vasotocin (VT) are the teleost homologues of these genes. A contiguous stretch of 46 kb spanning the Fugu IT-VT locus has been sequenced, and nine putative genes were found. Unlike the OT and vasopressin genes, which are closely linked in the mammalian genome in a tail-to-tail orientation, Fugu IT and VT genes are linked head to tail and are separated by five genes. When a cosmid containing the Fugu IT-VT locus was introduced into the rat genome, we found that the Fugu IT gene was specifically expressed in rat hypothalamic oxytocinergic neurons and mimicked the response of the endogenous OT gene to an osmotic stimulus. These data show that cis-acting elements and trans-acting factors mediating the cell-specific and physiological regulation of the OT and IT genes are conserved between mammals and fish. The combination of Fugu genome analysis and transgenesis in a mammal is a powerful tool for identifying and analyzing conserved vertebrate regulatory elements.