Cloning and Functional Analysis of Genes Governing Characteristics of Renal Glomerulus

肾小球的独特功能应该与其独特的结构和分子组成有关。为了了解肾小球的结构和功能特征，我们首先旨在确定这种结构中特异性存在的分子。我们采用差异筛选方法分离出在大鼠肾小球中主要表达的基因。目前已分离出几个在肾小球中主要或唯一表达的基因，包括：嗅觉素相关蛋白、胸腺素β4、肝素结合表皮生长因子、VE-cadherin、βCOP和IV型胶原α3链。一些新的基因也被分离为肾小球易感基因：14-1和17-3。此外，还发现了几个新的肾特异性或肾易感基因：Ig-Hepta、FR-67和CS-5。其中，对嗅素相关蛋白和Ig-Hepta进行了深入研究。olfactomedin相关蛋白定位于肾小球足细胞的高尔基体及其c端氨基酸序列，SDEL是高尔基保留信号。igg - hepta具有2个类igg结构域和7个跨膜结构域。该分子免疫定位于收集管的嵌入细胞中，提示其在酸碱平衡调节中起作用。

The unique function of renal glomerulus should be related to its unique structure and molecular components. To understand the structural and functional characteristics of renal glomerulus we first aimed to identify molecules which were specifically present in this structure. We employed differential screening methods to isolate genes which were predominantly expressed in rat glomerulus. Several genes have been isolated as those which were predominantly or uniquely expressed in the glomerulus although their sequences had been registered : olfactomedin-related protein, thymosin β4, heparin-binding epidermal growth factor, VE-cadherin, βCOP and collagen type IV α3 chain. A few novel genes were also isolated as glomerulus-prone ones : 14-1 and 17-3. In addition, several novel genes were identifed as kidney-specific or kidney-prone ones : Ig-Hepta, FR-67 and CS-5. Among them, olfactomedin-related protein and Ig-Hepta were intensively studied. Olfactomedin-related protein was localized in the Golgi apparatus of glomerular podocytes and its C-terminus amino acid sequence, SDEL was a Golgi-retension signal. Ig-Hepta had two Ig-like domains and 7 transmembrane domains. The molecule was immunolocalized in the intercalated cells in the collecting duccts, suggesting a role in acid-base balance regulation.