Cloning and Functional Analysis of Genes Governing Characteristics of Renal Glomerulus

肾小球独特的功能应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，我们首先旨在鉴定在该结构中特异性存在的分子。我们采用差异筛选方法分离主要在大鼠肾小球中表达的基因。已经分离出一些基因，这些基因主要或唯一地在肾小球中表达，尽管它们的序列已被注册：嗅觉调节素相关蛋白、胸腺素β4、肝素结合表皮生长因子、VE-钙粘蛋白、βCOP和IV型胶原α3链。一些新的基因也被分离为肾小球倾向的基因：14-1和17-3。此外，一些新的基因被确定为肾脏特异性或肾脏倾向的：Ig-Hepta，FR-67和CS-5。其中，嗅觉调节素相关蛋白和Ig-Hepta是研究较为集中的两个蛋白。嗅调节素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是高尔基体滞留信号。Ig-Hepta具有2个Ig样结构域和7个跨膜结构域。该分子免疫定位于集合管中的闰细胞，表明其在酸碱平衡调节中的作用。

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.