Murphy D, Si-Hoe S L, Brenner S, Venkatesh B
Department of Medicine, University of Bristol, Bristol Royal Infirmary, UK.
Bioessays. 1998 Sep;20(9):741-9. doi: 10.1002/(SICI)1521-1878(199809)20:9<741::AID-BIES7>3.0.CO;2-J.
The brain peptides vasopressin and oxytocin play crucial roles in the regulation of salt and water balance. The genes encoding these neurohormones are regulated by cell-specific and physiological cues, but the molecular mechanisms remain obscure. New strategies, involving the introduction of rat transgenes into rats, are being used to address these issues, but the complexity of the rat genome has hampered progress. By contrast, the pufferfish, Fugu rubripes, has a "junk-free" genome. The oxytocin homologue from Fugu, isotocin, has been introduced into rats and is expressed in oxytocin neurons, where it is upregulated by physiological perturbations that upregulate the oxytocin gene. The Fugu and rat lineages separated 400 million years ago, yet the mechanisms that regulate the isotocin and oxytocin genes have been conserved. Fugu genome analysis and transgenesis in the physiologically tractable rat host are a powerful combination that will enable the identification of fundamental components of the neural systems that control homeostasis.
大脑肽类物质血管加压素和催产素在盐和水平衡的调节中发挥着关键作用。编码这些神经激素的基因受细胞特异性和生理信号的调控，但其分子机制仍不清楚。涉及将大鼠转基因导入大鼠的新策略正被用于解决这些问题，但大鼠基因组的复杂性阻碍了研究进展。相比之下，河豚（红鳍东方鲀）拥有一个“无冗余”基因组。河豚的催产素同源物异催产素已被导入大鼠，并在催产素神经元中表达，在那里它会因上调催产素基因的生理扰动而被上调。河豚和大鼠的谱系在4亿年前就已分开，但调节异催产素和催产素基因的机制却得以保留。河豚基因组分析以及在生理上易于处理的大鼠宿主中进行转基因研究，是一种强大的组合，将有助于识别控制体内平衡的神经系统的基本组成部分。
