Normal CNS myelination in transgenic mice overexpressing MHC class I H-2L(d) in oligodendrocytes.
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.
Fuss
B
B
Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA. BFUSS@HSC.VCU.EDU
Afshari
F S
FS
Colello
R J
RJ
Macklin
W B
WB
D000375:Aging / Q000235:genetics; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured / Q000166:cytology / Q000378:metabolism; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005805:Genes, MHC Class I / Q000502:physiology*; D006183:H-2 Antigens / Q000235:genetics*; D064532:Histocompatibility Antigen H-2D; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
D000954:Antigens, Surface; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D018991:Myelin Proteolipid Protein; D012333:RNA, Messenger