Lie-Venema H, de Boer P A, Moorman A F, Lamers W H
Department of Anatomy and Embryology, University of Amsterdam, Academic Medical Centre, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Biochem J. 1997 May 1;323 ( Pt 3)(Pt 3):611-9. doi: 10.1042/bj3230611.
In mammals, glutamine synthetase (GS) is expressed in a large number of organs, but the precise regulation of its expression is still obscure. Therefore a detailed analysis of the activity of the upstream regulatory element of the GS gene in the transcriptional regulation of its expression was carried out in transgenic mice carrying the chloramphenicol acetyltransferase (CAT) gene under the control of the upstream regulatory region of the GS gene. CAT and GS mRNA expression were compared in liver, epididymis, lung, adipocytes, testis, kidney, skeletal muscle and gastrointestinal tract, both quantitatively by ribonuclease-protection analysis and topographically by in situ hybridization. It was found that the upstream regulatory region is active with respect both to the level and to the topography of GS gene expression in liver, epididymis, gastrointestinal tract (stomach, small intestine and colon) and skeletal muscle. On the other hand, in the kidney, brain, adipocytes, spleen, lung and testis, GS gene expression is not or only partly regulated by the 5' enhancer. A second enhancer, identified within the first intron, may regulate GS expression in the latter organs. Furthermore, CAT expression in the brain did not co-localize with that of GS, showing that the 5' regulatory region of the GS gene does not direct its expression to the astrocytes.
在哺乳动物中,谷氨酰胺合成酶(GS)在大量器官中表达,但其表达的精确调控仍不清楚。因此,在携带氯霉素乙酰转移酶(CAT)基因且该基因受GS基因上游调控区控制的转基因小鼠中,对GS基因上游调控元件在其表达转录调控中的活性进行了详细分析。通过核糖核酸酶保护分析定量比较了肝脏、附睾、肺、脂肪细胞、睾丸、肾脏、骨骼肌和胃肠道中CAT和GS mRNA的表达,并通过原位杂交进行了定位比较。结果发现,上游调控区在肝脏、附睾、胃肠道(胃、小肠和结肠)和骨骼肌中,对GS基因表达的水平和定位均具有活性。另一方面,在肾脏、大脑、脂肪细胞、脾脏、肺和睾丸中,GS基因表达不受5'增强子调控或仅部分受其调控。在第一个内含子中鉴定出的第二个增强子可能调控后一组器官中的GS表达。此外,大脑中CAT的表达与GS的表达不共定位,表明GS基因的5'调控区并未将其表达导向星形胶质细胞。