Studies on mechanisms of immediate osmotic adaptation in fish.

在这项研究中，我研究了鱼类体液渗透压针对环境水盐度突然变化的即时调节机制。研究集中在三个肽激素家族，即利尿钠肽（NP）家族、鸟苷素（GN）家族和肾上腺髓质素（AM）家族。至于NP家族，我和合作者发现鱼类中有7种NP亚型，而哺乳动物中只发现了3种亚型。通过青鳉、河豚和人类的比较基因组分析，以及青鳉和虹鳟鱼的连锁图谱，我们发现NP家族是通过两个步骤产生的：一是染色体复制，从单个祖先基因产生四个NP基因，另一个是串联复制，从四个NP基因之一产生额外的三个基因。至于GN家族，我们在鳗鱼中发现了3个配体和2个受体，而哺乳动物则有2个配体和1个受体。我们还表明，鳗鱼中三种配体基因的表达水平在海水中高于淡水中。至于AM家族，我们在河豚中发现了5个基因，而在哺乳动物中只发现了1个基因。利用河豚的序列和基因组信息，我们成功地从包括人类和小鼠在内的哺乳动物中发现了一种新的激素 AM2。此外，我们还尝试建立一种新的渗透适应研究实验模型。我们发现了一种下流的科蒂鱼，Cottus kazika 应该是一个很好的模型。

In this study, I studied mechanism of immediate regulation of the body fluid osmolality in fish against sudden changes in salinity of environmental water. Studies were focused on three peptide hormone families, the natriuretic peptide (NP) family, guanylin (GN) family and adrenomedullin (AM) family. As for NP family, I and collaborators found seven NP subtypes exist in fish whereas only three subtypes have been found in mammals. By comparative genomic analysis, among the medaka, pufferfishes and human, and linkage mapping in the medaka and rainbow trout, we found that the NP family has been generated through two steps : one is the chromosomal duplications that generated four NP sgenes from a single ancestral gene and the other is tandem duplications that generated additional three genes from one of the four NP genes. As for GN family, we found three ligands and two receptors in the eel whereas mammals have two ligands and one receptor. We also showed that the expression levels of the three ligand genes are higher in seawater than in fresh water in the eel. As for AM family, we found five genes from the pufferfish whereas only one gene has been found in mammals. Using the sequence and genomic information in the pufferfish, we successfully found a new hormone, AM2 from mammals including human and mouse. In addition, we have been attempted to establish a new experimental model for osmotic adaptation studies. We found a catadromous cottid fish, Cottus kazika should be a good model.