Johnson R S, Roder J C, Riordan J R
Department of Biochemistry, University of Toronto, Hospital for Sick Children, Ontario, Canada.
J Neurochem. 1995 Mar;64(3):967-76. doi: 10.1046/j.1471-4159.1995.64030967.x.
We have created transgenic mice bearing varying copy numbers of a transgene coding for normal DM-20, the alternatively spliced quantitatively minor isoform of myelin proteolipid protein. Demyelination of the CNS occurs as a consequence of 70 copies of this transgene. Overt symptoms begin at approximately 3 months with a wobbling gait. Occasional seizures lasting a few seconds begin at 3-4 months. These symptoms progress in severity with age. Death occurs by 8-10 months. Myelination in 2-month-old animals, before the onset of any overt symptoms, appears morphologically normal at the electron microscopic level. However, the myelin in these 2-month-old animals has a reduced amount of the major myelin proteolipid protein and about three times as much DM-20 as normal animals. In 7-month-old animals that appear to be undergoing demyelination in the CNS, both the major myelin proteolipid protein and DM-20 are greatly reduced relative to the 2-month-old animal. Mice with 17 copies of the transgene also have a reduced amount of the major myelin proteolipid protein but appear to be otherwise normal and have normal life spans (> 2 yr). Mice with low copy numbers of the transgene (2-4 copies) appear to be unaffected and have normal life spans.
我们培育出了携带不同拷贝数转基因的小鼠，该转基因编码正常的DM-20，即髓磷脂蛋白脂蛋白的可变剪接定量次要异构体。由于该转基因有70个拷贝，中枢神经系统会发生脱髓鞘。明显的症状大约在3个月时开始出现，表现为步态摇晃。3至4个月时开始偶尔出现持续几秒的癫痫发作。这些症状会随着年龄的增长而加重。8至10个月时小鼠会死亡。在2个月大的动物中，在任何明显症状出现之前，电子显微镜水平下的髓鞘形成在形态上看起来正常。然而，这些2个月大动物的髓鞘中主要髓磷脂蛋白脂蛋白的含量减少，且DM-20的含量约为正常动物的三倍。在7个月大的动物中，中枢神经系统似乎正在发生脱髓鞘，相对于2个月大的动物，主要髓磷脂蛋白脂蛋白和DM-20的含量都大大减少。携带17个拷贝转基因的小鼠主要髓磷脂蛋白脂蛋白的含量也减少，但在其他方面似乎正常，寿命正常（>2年）。携带低拷贝数转基因（2至4个拷贝）的小鼠似乎未受影响，寿命正常。
