Fuss B, Afshari F S, Colello R J, Macklin W B
Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
Mol Cell Neurosci. 2001 Aug;18(2):221-34. doi: 10.1006/mcne.2001.1011.
In demyelinating diseases, such as multiple sclerosis, an upregulation of MHC class I expression is thought to contribute to oligodendrocyte/myelin damage. In order to investigate potential physiological consequences of upregulated MHC class I expression in oligodendrocytes, we generated transgenic mice that overexpress H-2L(d) under the control of the proteolipid protein (PLP) promoter (PLP-L(d) mice). We focused our studies on the MHC class I molecule H-2L(d), because of its unique intracellular transport characteristics. In the CNS of PLP-L(d) mice, H-2L(d) was expressed by oligodendrocytes. Furthermore, H-2L(d) protein was transported to and expressed on the surface of oligodendrocytes. Most importantly, this upregulation of MHC class I expression in the CNS of PLP-L(d) mice did not by itself result in a de- or dysmyelinating phenotype. These transgenic mice are likely to provide a unique and novel tool for the analysis of potential roles of MHC class I-mediated mechanisms in demyelinating pathologies.
在脱髓鞘疾病中，如多发性硬化症，MHC I类分子表达上调被认为会导致少突胶质细胞/髓鞘损伤。为了研究少突胶质细胞中MHC I类分子表达上调可能产生的生理后果，我们构建了在蛋白脂质蛋白（PLP）启动子控制下过表达H-2L(d)的转基因小鼠（PLP-L(d)小鼠）。由于其独特的细胞内运输特性，我们将研究重点放在MHC I类分子H-2L(d)上。在PLP-L(d)小鼠的中枢神经系统中，少突胶质细胞表达H-2L(d)。此外，H-2L(d)蛋白被转运至少突胶质细胞表面并在其上表达。最重要的是，PLP-L(d)小鼠中枢神经系统中MHC I类分子表达的这种上调本身并未导致脱髓鞘或髓鞘形成异常的表型。这些转基因小鼠可能为分析MHC I类介导的机制在脱髓鞘病变中的潜在作用提供一种独特而新颖的工具。
