Normal CNS myelination in transgenic mice overexpressing MHC class IH-2L(d) in oligodendrocytes

In demyelinating diseases, such as multiple sclerosis, an upregulation of M HC class I expression is thought to contribute to oligodendrocyte/myelin da mage. In order to investigate potential physiological consequences of upreg ulated 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 mo lecule H-2L(d), because of its unique intracellular transport characteristi cs. 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 surfac e of oligodendrocytes. Most importantly, this upregulation of MHC class I e xpression in the CNS of PLP-L-d mice did not by itself result in a de- or d ysmyelinating phenotype. These transgenic mice are likely to provide a uniq ue and novel tool for the analysis of potential roles of MHC class I-mediat ed mechanisms in demyelinating pathologies.