Rat lactase-phlorizin hydrolase human growth hormone transgene is expressed on small intestinal villi in transgenic mice
Rat lactase-phlorizin hydrolase human growth hormone transgene is expressed on small intestinal villi in transgenic mice
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DOI：
10.1016/s0016-5085(97)70179-3
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发表时间：
1997-09-01
期刊：
影响因子：
29.4
通讯作者：
Verhave, M
中科院分区：
文献类型：
--
作者：
Krasinski, SD;Upchurch, BH;Verhave, M
背景和目标：乳糖酶根皮苷水解酶（LPH）是一种肠细胞特异性的吸收性基因，其表达模式沿着隐窝-绒毛（垂直）、近端-远端（水平）和发育（时间）梯度。本研究的目的是表征大鼠LPH基因内的调控元件的能力，以指导适当的细胞谱系和地形图模式的表达在转基因小鼠体内。研究方法：使用含有与人生长激素报告基因融合的大鼠LPH基因的碱基-2038至+15的构建体建立转基因小鼠系。结果：在一个品系中，转基因只在小肠中表达，并定位于绒毛上的吸收性肠上皮细胞。转基因不表达在杯状或肠内分泌细胞或隐窝。转基因表达沿着水平和发育梯度是不同的，从本地小鼠LPH基因。结论：结果表明，大鼠LPH基因的-2038至+15区域包含指导正确组织、细胞和垂直表达的调控元件，但可能不包含适当水平和时间控制所需的所有元件。这项调查提供了进一步了解肠道基因表达的分子控制的复杂性。
Background & Aims: Lactase-phlorizin hydrolase (LPH) is an absorptive enterocyte-specific gene that is expressed in a well-characterized pattern along the crypt-villus (vertical), proximal-distal (horizontal), and developmental (temporal) gradients. The aim of this study was to characterize the capacity of regulatory elements within the rat LPH gene to direct appropriate cell lineage and topographical patterns of expression in vivo in transgenic mice. Methods: Transgenic mouse lines were established using a construction containing bases -2038 to +15 of the rat LPH gene fused to a human growth hormone reporter gene. Results: In one line, the transgene was expressed only in small intestine and was localized to absorptive enterocytes on villi. The transgene was not expressed in goblet or enteroendocrine cells or in crypts. Transgene expression along horizontal and developmental gradients was different from that of the native mouse LPH gene. Conclusions: The results suggest that the region from -2038 to +15 of the rat LPH gene contains regulatory elements that direct correct tissue, cell, and vertical expression but may not contain all the elements necessary for appropriate horizontal and temporal control. This investigation provides further insight into the complexities of the molecular control of intestinal gene expression.