Reiner O, Horowitz M
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Gene. 1988 Dec 20;73(2):469-78. doi: 10.1016/0378-1119(88)90511-2.
Gaucher disease is an inborn error of sphingolipid metabolism. It is due to decreased enzymatic activity of glucocerebrosidase (GCase) which causes accumulation of glucocerebrosides, mainly in cells of the reticulo-endothelial system. The disorder is clinically heterogenous and can include central nervous system signs. However, the manifestations of the disease in most cases are restricted to a limited number of cell types and organs. This could be explained by highly differential expression of the human gcs gene. To test this notion, the level of GCase-specific mRNA was determined in different human cell lines by hybridizing Northern blots to a human GCase-specific cDNA probe or by using the RNase protection method. It was found that epithelial cells exhibit high levels of GCase mRNA while skin fibroblasts and promyelocytes show intermediate steady-state levels of this RNA. Macrophages have low steady-state levels of GCase mRNA and in B-cells it is hardly detectable. Moreover, when B-cells or skin fibroblasts were transfected with a vector harbouring the bacterial cat gene coupled to the human gcs gene promoter, the levels of CAT expressed in each cell type were directly correlated to the amount of endogenous GCase RNA. Comparison of the GCase mRNA levels in Gaucher-versus non-Gaucher-derived cells revealed that in Gaucher cells this RNA is always more abundant than in the corresponding non-Gaucher counterparts, suggesting the involvement of a feed-back mechanism sensitive to the levels of actual enzymatic activity.
戈谢病是一种鞘脂代谢的先天性缺陷。它是由于葡萄糖脑苷脂酶（GCase）的酶活性降低，导致葡萄糖脑苷脂积累，主要在网状内皮系统的细胞中。该疾病在临床上具有异质性，可包括中枢神经系统症状。然而，在大多数情况下，该疾病的表现仅限于有限数量的细胞类型和器官。这可以通过人类gcs基因的高度差异表达来解释。为了验证这一观点，通过将Northern印迹与人类GCase特异性cDNA探针杂交或使用核糖核酸酶保护法，测定了不同人类细胞系中GCase特异性mRNA的水平。发现上皮细胞表现出高水平的GCase mRNA，而皮肤成纤维细胞和早幼粒细胞显示出该RNA的中等稳态水平。巨噬细胞的GCase mRNA稳态水平较低，在B细胞中几乎检测不到。此外，当用携带与人类gcs基因启动子偶联的细菌cat基因的载体转染B细胞或皮肤成纤维细胞时，每种细胞类型中表达的CAT水平与内源性GCase RNA的量直接相关。比较戈谢病来源细胞与非戈谢病来源细胞中的GCase mRNA水平发现，在戈谢病细胞中，这种RNA总是比相应的非戈谢病细胞更丰富，这表明存在一种对实际酶活性水平敏感的反馈机制。
