Krasinski S D, Upchurch B H, Irons S J, June R M, Mishra K, Grand R J, Verhave M
Department of Pediatrics, Boston Floating Hospital, New England Medical Center Hospitals, Massachusetts, USA.
Gastroenterology. 1997 Sep;113(3):844-55. doi: 10.1016/s0016-5085(97)70179-3.
BACKGROUND & AIMS: Lactase-phlorizin hydrolase (LPH) is an absorptive enterocyte-specific gene that is expressed in a well-characterized pattern along the cryptvillus (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.
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.
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.
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.
乳糖酶 - 根皮苷水解酶(LPH)是一种吸收性肠上皮细胞特异性基因,其沿着隐窝 - 绒毛(垂直)、近端 - 远端(水平)和发育(时间)梯度以一种特征明确的模式表达。本研究的目的是鉴定大鼠LPH基因内调控元件在转基因小鼠体内指导合适的细胞谱系和表达的地形模式的能力。
使用包含大鼠LPH基因 -2038至 +15碱基并与人生长激素报告基因融合的构建体建立转基因小鼠品系。
在一个品系中,转基因仅在小肠中表达,并定位于绒毛上的吸收性肠上皮细胞。转基因在杯状细胞或肠内分泌细胞以及隐窝中不表达。转基因沿水平和发育梯度的表达与天然小鼠LPH基因不同。
结果表明,大鼠LPH基因 -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。本研究进一步深入了解了肠道基因表达分子控制的复杂性。