Verghese George M, Tong Z Y, Bhagwandin Vikash, Caughey George H
Department of Medicine, University of Virginia, Charlottesville, Virginia 22908-0546, USA.
Am J Respir Cell Mol Biol. 2004 Apr;30(4):519-29. doi: 10.1165/rcmb.2003-0251OC. Epub 2003 Sep 4.
Human prostasin is a membrane-anchored serine peptidase hypothesized to regulate lung epithelial sodium transport. It belongs to a unique family of genes on chromosome 16p11.2/13.3. Here we describe genomic cloning, promoter analysis, and expression of prostasin's mouse ortholog. The 4.3-kb mouse prostasin gene (prss8) has a six-exon organization identical to human prostasin. Prss8 spans two signal tagged-sites localized to chromosome 7. Multiple mRNA transcripts arise from two consensus initiator elements of a TATA-less promoter and an alternatively spliced, 5' untranslated region intron. Reporter assay establishes that the initiator elements and a GC-rich domain comprise the core promoter and identifies 5' flanking regions with strong enhancer and repressor activity. The 3' untranslated region overlaps the 3' untranslated region of the Myst1 gene oriented tail-to-tail at this locus. Prss8 is highly transcribed in pancreas, kidney, submaxillary gland, lung, thyroid, prostate, and epididymis, and is developmentally regulated. Using selective riboprobes and antibodies to mouse prostasin, we localized its expression to lung airway epithelial and alveolar type II cells and kidney cortical tubule epithelium. Mouse prostasin highly resembles its human ortholog in gene organization and tissue specificity, including strong expression in pulmonary epithelium, suggesting that mice will be useful for probing prostasin's functions in vivo.
人前列腺素是一种膜锚定丝氨酸蛋白酶，据推测可调节肺上皮钠转运。它属于位于16p11.2/13.3染色体上的一个独特基因家族。在此我们描述前列腺素小鼠直系同源基因的基因组克隆、启动子分析及表达。4.3kb的小鼠前列腺素基因（prss8）具有与人类前列腺素相同的六外显子结构。Prss8跨越两个定位于7号染色体的信号标签位点。多个mRNA转录本源自一个无TATA启动子的两个共有起始元件以及一个可变剪接的5'非翻译区内含子。报告基因检测表明起始元件和一个富含GC的结构域构成核心启动子，并鉴定出具有强增强子和抑制子活性的5'侧翼区域。3'非翻译区与该位点处Myst1基因的3'非翻译区尾对尾重叠。Prss8在胰腺、肾脏、颌下腺、肺、甲状腺、前列腺和附睾中高度转录，且受发育调控。使用针对小鼠前列腺素的选择性核糖探针和抗体，我们将其表达定位到肺气道上皮细胞和II型肺泡细胞以及肾皮质肾小管上皮。小鼠前列腺素在基因结构和组织特异性方面与人类直系同源基因高度相似，包括在肺上皮中的强表达，这表明小鼠将有助于在体内探究前列腺素的功能。
