Study of Human-Specific Microglial Receptor Siglec-11 and Generation of Transgenic Mice Expressing Human Siglec-11
Study of Human-Specific Microglial Receptor Siglec-11 and Generation of Transgenic Mice Expressing Human Siglec-11
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dc.contributor.advisor | Neumann, Harald | |
dc.contributor.author | Wang, Yiner | |
dc.date.accessioned | 2020-04-14T01:10:30Z | |
dc.date.available | 2020-04-14T01:10:30Z | |
dc.date.issued | 07.07.2009 | |
dc.identifier.uri | https://hdl.handle.net/20.500.11811/4097 | |
dc.description.abstract | Siglec-11 is a recently identified human-specific CD33-related Siglec expressed on microglia. The full-length cDNA of Siglec-11 encodes 5 extracellular Ig-like domains, a single pass transmembrane domain, and a cytosolic tail, which contains ITIMs. In human, histopathology demonstrated the expression of Siglec-11 on tissue macrophages in various tissues, including microglia in brain. We studied Siglec-11 in microglia. A Siglec-11 splice variant, but no full length Siglec-11 was identified in human brain tissue samples. Functional analysis was performed in cultured mouse microglial cells lentivirally transduced with this splice variant of human Siglec-11. Under stimulation with LPS, gene transcription of IL-1β and NOS2 of microglia was reduced after cross-linking of Siglec-11. The Aβ phagocytosis ability was impaired in Siglec-11 expressing microglia. PSA-NCAM as a putative ligand of Siglec-11 was detected on microglia and neurons. Co-culture of microglia expressing Siglec-11 and neurons demonstrated neuroprotective function of Siglec-11. Neurite density and neuronal cell body density were higher in co-cultures with Siglec-11 expressing microglia than those of control co-cultures. Neuroprotective effect was dependent on sialic acid residues on neurons, but independent on polysialylated residues of microglia. Transgenic mice were generated expressing Siglce-11 under the microglial Iba1-promoter. Chimeric mice were obtained from aggregation of genetically modified ES cells and embryos, but no germline transmission was achieved. Germline transmission was obtained from pronuclear injection of Siglec-11 DNA. Several strains of transgenic mice expressing Siglec-11 in the brain have been sucessfully established. Thus, data show that Siglec-11 is an inhibitory receptor of microglia that might help to create an immunosuppressive milieu in the CNS and alleviate microglial neurotoxicity. Humanized transgenic mice expressing Siglec-11 we have generated serve as a good model to provide valuble information on the natural features of Siglec-11. | |
dc.language.iso | eng | |
dc.rights | In Copyright | |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | Neurobiologie | |
dc.subject.ddc | 570 Biowissenschaften, Biologie | |
dc.title | Study of Human-Specific Microglial Receptor Siglec-11 and Generation of Transgenic Mice Expressing Human Siglec-11 | |
dc.type | Dissertation oder Habilitation | |
dc.publisher.name | Universitäts- und Landesbibliothek Bonn | |
dc.publisher.location | Bonn | |
dc.rights.accessRights | openAccess | |
dc.identifier.urn | https://nbn-resolving.org/urn:nbn:de:hbz:5N-18095 | |
ulbbn.pubtype | Erstveröffentlichung | |
ulbbnediss.affiliation.name | Rheinische Friedrich-Wilhelms-Universität Bonn | |
ulbbnediss.affiliation.location | Bonn | |
ulbbnediss.thesis.level | Dissertation | |
ulbbnediss.dissID | 1809 | |
ulbbnediss.date.accepted | 25.06.2009 | |
ulbbnediss.fakultaet | Mathematisch-Naturwissenschaftliche Fakultät | |
dc.contributor.coReferee | Kolanus, Waldemar |
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