Reference - Detail
| RRC ID | 17664 |
|---|---|
| Author | Satoh J, Shimamura Y, Tabunoki H. |
| Title | Gene expression profile of THP-1 monocytes following knockdown of DAP12, a causative gene for Nasu-Hakola disease. |
| Journal | Cell Mol Neurobiol |
| Abstract |
Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, is a rare autosomal recessive disorder characterized by progressive presenile dementia and formation of multifocal bone cysts, caused by a loss-of-function mutation of DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor complex expressed on osteoclasts, dendritic cells, macrophages, monocytes, and microglia. At present, the precise molecular mechanisms underlying development of leukoencephalopathy and bone cysts in NHD remain largely unknown. We established THP-1 human monocyte clones that stably express small interfering RNA targeting DAP12 for serving as a cellular model of NHD. Genome-wide transcriptome analysis identified a set of 22 genes consistently downregulated in DAP12 knockdown cells. They constituted the molecular network closely related to the network defined by cell-to-cell signaling and interaction, hematological system development and function, and inflammatory response, where NF-κB acts as a central regulator. These results suggest that a molecular defect of DAP12 in human monocytes deregulates the gene network pivotal for maintenance of myeloid cell function in NHD. |
| Volume | 32(3) |
| Pages | 337-43 |
| Published | 2012-4-1 |
| DOI | 10.1007/s10571-011-9769-z |
| PMID | 22080356 |
| MeSH | Adaptor Proteins, Signal Transducing / antagonists & inhibitors Adaptor Proteins, Signal Transducing / deficiency Adaptor Proteins, Signal Transducing / genetics* Cell Line, Tumor Down-Regulation / genetics Gene Knockdown Techniques / methods Gene Regulatory Networks / genetics Humans Lipodystrophy / diagnosis Lipodystrophy / genetics* Lipodystrophy / pathology* Membrane Proteins / antagonists & inhibitors Membrane Proteins / deficiency Membrane Proteins / genetics* Monocytes / metabolism* Monocytes / pathology* Myeloid Cells / metabolism Myeloid Cells / pathology Osteochondrodysplasias / diagnosis Osteochondrodysplasias / genetics* Osteochondrodysplasias / pathology* RNA, Small Interfering / genetics Subacute Sclerosing Panencephalitis / diagnosis Subacute Sclerosing Panencephalitis / genetics* Subacute Sclerosing Panencephalitis / pathology* Transcriptome / genetics* |
| IF | 3.606 |
| Times Cited | 6 |
| WOS Category | NEUROSCIENCES CELL BIOLOGY |
| Resource | |
| Human and Animal Cells | THP-1(RCB1189) |