Hergersberg M, Matsuo K, Gassmann M, Schaffner W, Lüscher B, Rülicke T, Aguzzi A
Institut für Medizinische Genetik, Universität Zürich, Switzerland.
Hum Mol Genet. 1995 Mar;4(3):359-66. doi: 10.1093/hmg/4.3.359.
Fragile X syndrome is one of the most common genetic causes of mental retardation, yet the mechanisms controlling expression of the fragile X mental retardation gene FMR1 are poorly understood. To identify sequences regulating FMR1 transcription, transgenic mouse lines were established using a fusion gene consisting of an E.coli beta-galactosidase reporter gene (lacZ) linked to a 2.8 kb fragment spanning the 5'-region of FMR1. Five transgenic mouse lines showed lacZ expression in brain, in particular in neurons of the hippocampus and the granular layer of the cerebellum. Expression of the reporter gene was also detected in Leydig cells and spermatogonia in the testis, in many epithelia of adult mice, and in the two other steroidogenic cell types, adrenal cortex cells and ovarian follicle cells. Embryonic tissues which showed strong activity of the reporter gene included the telencephalon, the genital ridge, and the notochord. This expression pattern closely resembles the endogenous one, indicating that the 5' FMR1 gene promoter region used in this study contains most cis-acting elements regulating FMR1 transcription.
脆性X综合征是智力迟钝最常见的遗传病因之一，然而，控制脆性X智力迟钝基因FMR1表达的机制却鲜为人知。为了鉴定调控FMR1转录的序列，构建了转基因小鼠品系，所用的融合基因由一个大肠杆菌β-半乳糖苷酶报告基因（lacZ）与一个跨越FMR1 5′区域的2.8kb片段相连组成。五个转基因小鼠品系在脑中呈现lacZ表达，特别是在海马体神经元和小脑颗粒层。报告基因在睾丸的Leydig细胞和精原细胞、成年小鼠的许多上皮组织以及另外两种类固醇生成细胞类型（肾上腺皮质细胞和卵巢卵泡细胞）中也有表达。报告基因显示强活性的胚胎组织包括端脑、生殖嵴和脊索。这种表达模式与内源性表达模式非常相似，表明本研究中使用的FMR1基因5′启动子区域包含了调控FMR1转录的大多数顺式作用元件。
