Normal CNS myelination in transgenic mice overexpressing MHC class IH-2Ld in oligodendrocytes
Normal CNS myelination in transgenic mice overexpressing MHC class IH-2Ld in oligodendrocytes
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DOI：
10.1006/mcne.2001.1011
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发表时间：
2001-08-01
影响因子：
3.5
通讯作者：
Macklin, WB
中科院分区：
文献类型：
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作者：
Fuss, B;Afshari, FS;Macklin, WB
在多发性硬化症等脱髓鞘疾病中，MHC I类分子表达上调被认为是导致少突胶质细胞/髓鞘损伤的原因之一。为了研究MHC-I类分子在少突胶质细胞中表达上调的潜在生理后果，我们建立了在蛋白脂蛋白(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MHC I类分子H-2L(D)具有独特的细胞内转运特性，我们对其进行了重点研究。在PLP-L-d小鼠的中枢神经系统中，H-2L(D)由少突胶质细胞表达。此外，H-2L(D)蛋白被转运到少突胶质细胞表面并在其表面表达。最重要的是，PLP-L-d小鼠中枢神经系统中MHC-I类表达的上调本身并没有导致髓鞘脱失或髓鞘障碍的表型。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理中的潜在作用提供了一种独特的新工具。
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.