Camacho-Hübner A, Beermann F
Swiss Institute for Experimental Cancer Research (ISREC), Epalinges, Switzerland.
Genesis. 2001 Apr;29(4):180-7. doi: 10.1002/gene.1022.
In this study, we have addressed the impact of the mouse tyrosinase enhancer on regulated expression from the mouse tyrosinase promoter during embryonic development. Stable and transient transgenic experiments using the reporter gene lacZ reveal that (1) expression is detected in neural crest-derived melanoblasts from E11.5 onward, (2) the enhancer does not increase transgenic expression in optic cup-derived pigment cells of the retinal pigment epithelium (RPE), and (3) expression in the telencephalon is not any longer detected. The importance of the enhancer for expression in pigment cells of the eye was further investigated in adult mice using an attenuated diphtheria toxin A gene. This demonstrated that in presence of the enhancer the transgene expression is specifically targeted to neural crest-derived melanocytes of the choroid and not, or slightly, to the RPE. This suggests that tyrosinase is differentially regulated in the two pigment cell lineages, and that this promoter can be used to target expression preferentially to the neural crest-derived melanocyte lineage.
在本研究中,我们探讨了小鼠酪氨酸酶增强子对胚胎发育过程中小鼠酪氨酸酶启动子调控表达的影响。使用报告基因lacZ进行的稳定和瞬时转基因实验表明:(1)从胚胎第11.5天起,在神经嵴来源的黑素母细胞中可检测到表达;(2)该增强子不会增加视网膜色素上皮(RPE)视杯来源色素细胞中的转基因表达;(3)在端脑中不再检测到表达。利用减毒白喉毒素A基因在成年小鼠中进一步研究了该增强子对眼部色素细胞表达的重要性。这表明,在存在增强子的情况下,转基因表达特异性靶向脉络膜神经嵴来源的黑素细胞,而非RPE细胞,或仅有轻微靶向RPE细胞。这表明酪氨酸酶在两种色素细胞谱系中受到不同调控,并且该启动子可用于将表达优先靶向神经嵴来源的黑素细胞谱系。