Markowitz A J, Wu G D, Birkenmeier E H, Traber P G
Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia.
Am J Physiol. 1993 Sep;265(3 Pt 1):G526-39. doi: 10.1152/ajpgi.1993.265.3.G526.
Sucrase-isomaltase (SI) is an enterocyte-specific gene that is expressed in complex developmental and spatial patterns. In this study, we examine the ability of regulatory elements within the human SI (hSI) gene to direct appropriate cell lineage and spatial patterns of expression in transgenic mice. Transgenic mouse lines were established using a construct containing bases -3424 to +54 of the hSI gene linked to the human growth hormone (hGH) structural gene. In each transgenic line, hGH mRNA and protein were expressed only in the small intestine and colon. In contrast to the endogenous mouse SI (mSI) gene, which was expressed along the entire length of the small intestine, hGH mRNA expression was predominantly found in the distal jejunum and ileum, with very low levels in more proximal portions of the small intestine. However, the pattern of transgene expression along the small intestinal crypt-villus axis was identical to the pattern of the endogenous mSI gene. These results suggest that regulatory elements necessary for intestine-specific transcription and differential expression along the intestinal crypt-villus axis are included in the 5'-flanking region of the hSI gene. Furthermore, these data suggest that different DNA regulatory regions regulate transcription along the horizontal intestinal axis. In the colon, there was aberrant expression of hGH in a subpopulation of enteroendocrine cells that contained peptide tyrosine tyrosine (PYY). This suggests that there are DNA regulatory elements, missing in the transgene construct, which normally suppress expression of the endogenous mSI gene in these cells. Taken together, these findings define the SI gene as a useful model for studies of differentiation, cell lineage determination, and mechanisms of complex spatial gene expression in the intestine.
蔗糖酶-异麦芽糖酶（SI）是一种肠上皮细胞特异性基因，以复杂的发育和空间模式表达。在本研究中，我们检测了人类SI（hSI）基因内调控元件在转基因小鼠中指导适当细胞谱系和表达空间模式的能力。使用包含hSI基因-3424至+54碱基并与人生长激素（hGH）结构基因相连的构建体建立转基因小鼠品系。在每个转基因品系中，hGH mRNA和蛋白仅在小肠和结肠中表达。与在内小肠全长表达的内源性小鼠SI（mSI）基因不同，hGH mRNA表达主要见于空肠远端和回肠，在小肠更近端部分水平极低。然而，转基因沿小肠隐窝-绒毛轴的表达模式与内源性mSI基因的模式相同。这些结果表明，hSI基因5'侧翼区域包含小肠特异性转录和沿小肠隐窝-绒毛轴差异表达所需的调控元件。此外，这些数据表明不同的DNA调控区域调节沿水平肠轴的转录。在结肠中，含有肽YY（PYY）的肠内分泌细胞亚群中hGH出现异常表达。这表明转基因构建体中缺失的DNA调控元件通常抑制这些细胞中内源性mSI基因的表达。综上所述，这些发现将SI基因定义为研究肠道分化、细胞谱系确定以及复杂空间基因表达机制的有用模型。
