Abstract
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is a recessively inherited disease characterized by early onset dementia associated with bone cysts. Our group has recently established the molecular background of PLOSL by identifying mutations in DAP12 and TREM2 genes. To understand how loss of function of the immune cell activating DAP12/TREM2 signaling complex leads to dementia and loss of myelin, we have analyzed here Dap12 and Trem2 expression in the mouse CNS. We show that Dap12 and Trem2 are expressed from embryonic stage to adulthood, and demonstrate a highly similar expression pattern. In addition, we identify microglial cells and oligodendrocytes as the major Dap12/Trem2-producing cells in the CNS and, consequently, as the predominant cell types involved in PLOSL pathogenesis. These findings provide a good starting point for the study of the molecular mechanisms of this inherited dementia and new evidence for the involvement of the immune system in neuronal degeneration.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / immunology*
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Animals, Newborn
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Antigens, Differentiation / metabolism
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Biomarkers
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Cells, Cultured
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Central Nervous System / embryology
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Central Nervous System / immunology*
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Central Nervous System / metabolism
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Dementia / immunology
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Dementia / metabolism
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Dementia / physiopathology
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Demyelinating Diseases / immunology
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Demyelinating Diseases / metabolism
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Demyelinating Diseases / physiopathology
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Gene Expression Regulation, Developmental / physiology
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Immunity, Innate / immunology*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred C57BL
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Microglia / metabolism
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Neurodegenerative Diseases / immunology*
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / physiopathology
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Oligodendroglia / metabolism
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Rats
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology*
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Receptors, Immunologic / metabolism
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Syndrome
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Differentiation
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Biomarkers
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Membrane Glycoproteins
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Receptors, Immunologic
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Tyrobp protein, mouse
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monocyte-macrophage differentiation antigen