Taniike M, Marcus J R, Nishigaki T, Fujita N, Popko B, Suzuki K, Suzuki K
Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, 27599-7525, USA.
J Neurosci Res. 1998 Feb 15;51(4):536-40. doi: 10.1002/(SICI)1097-4547(19980215)51:4<536::AID-JNR13>3.0.CO;2-1.
The developmental changes in expression of steady-state mRNA that encode proteins that are important for myelination (myelin basic protein, myelin-associated glycoprotein, proteolipid protein, UDP-galactose: ceramide galactosyltransferase) and glial fibrillary acidic protein were investigated in the brain of the twitcher mouse, a model of human globoid cell leukodystrophy. This disease is caused by a mutation in the gene encoding the lysosomal enzyme, galactosylceramidase, which catalyzes the degradation of the myelin lipid galactosylceramide. Before postnatal day (PND) 20, the levels of myelin protein mRNA were similar in twitcher and normal mice. With progression of demyelination after PND 25-30, myelin protein mRNA levels gradually decreased. The period of maximum expression of the myelin protein genes in twitcher mice was, however, similar to that of normal control mice. mRNA levels for the gene that encodes the enzyme UDP-galactose:ceramide galactosyltransferase which is responsible for catalyzing the final step in galactosylceramide synthesis, was exceptionally down-regulated from the early stages of the disease. The increase of glial fibrillary acidic protein (GFAP) mRNA levels preceded morphological evidence of demyelination.
在人类球状细胞脑白质营养不良模型——颤抖小鼠的大脑中，研究了编码对髓鞘形成重要的蛋白质（髓鞘碱性蛋白、髓鞘相关糖蛋白、蛋白脂蛋白、UDP-半乳糖：神经酰胺半乳糖基转移酶）以及胶质纤维酸性蛋白的稳态mRNA表达的发育变化。这种疾病是由编码溶酶体酶半乳糖神经酰胺酶的基因突变引起的，该酶催化髓鞘脂质半乳糖神经酰胺的降解。在出生后第20天（PND 20）之前，颤抖小鼠和正常小鼠的髓鞘蛋白mRNA水平相似。在出生后第25 - 30天之后随着脱髓鞘的进展，髓鞘蛋白mRNA水平逐渐下降。然而，颤抖小鼠中髓鞘蛋白基因的最大表达期与正常对照小鼠相似。负责催化半乳糖神经酰胺合成最后一步的酶UDP-半乳糖：神经酰胺半乳糖基转移酶的基因mRNA水平从疾病早期就异常下调。胶质纤维酸性蛋白（GFAP）mRNA水平的增加先于脱髓鞘的形态学证据出现。
