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Understanding the role of SATB1 in CD4+ T cells by analysis of conditionally targeted mice generated by genetic engineering

dc.contributor.advisorBeyer, Marc
dc.contributor.authorSommer, Daniel
dc.date.accessioned2020-04-25T13:42:58Z
dc.date.available2020-04-25T13:42:58Z
dc.date.issued12.12.2018
dc.identifier.urihttps://hdl.handle.net/20.500.11811/7677
dc.description.abstractSpecial-AT-rich-binding protein 1 (SATB1) is a nuclear protein providing higher order chromatin organization and regulation of gene expression, especially in T cells. In regulatory T cells, SATB1 is repressed to maintain Treg cell phenotype and function, whereas expression of SATB1 is associated with effector T cell responses. However, the overall impact of SATB1 on peripheral T cell function is still poorly understood, mainly due to a lack of appropriate in vivo models, as removal of SATB1 in mice has detrimental effects on T cell development and survival of the model organism. To address this issue and to gain a comprehensive picture of the function of SATB1 in peripheral CD4+ T cells, two mouse models were generated during this thesis, which allow for spatiotemporally controlled removal (SATB1-Flex KO) and induction (SATB1-KI) of the Satb1 gene specifically in peripheral CD4+ T cells. One of these mouse models was generated by a novel genome engineering approach, whereby we could demonstrate that TALEN-assisted gene targeting can facilitate the site-directed integration of even complex targeting constructs into the genome, thus allowing a facile generation of complex genetically modified mouse models.
Analysis of the SATB1-Flex KO model revealed new insights into the biological function of SATB1 in CD4+ T cell function, as it showed a yet unknown impact of SATB1 on the phenotypic switch from non-pathogenic to pathogenic TH17 cells, while the differentiation into the classical effector T cell subsets TH1, TH2 and non-pathogenic TH17 was not impaired by the removal of SATB1.
In contrast to that, the approach to evaluate the function of SATB1 in Treg cells using the SATB1-KI model is not suitable, as the apparent reprogramming of Treg cells hypothesized from a subset of exFoxp3 cells identified in this model is probably due to unspecific Cre-activity, rather than a SATB1-mediated effect. However, further analysis of the origin of these exFoxp3 cells might enable new insights into the role of SATB1 and Foxp3 during Treg cell development in the thymus.
dc.language.isoeng
dc.rightsIn Copyright
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectImmunsystem
dc.subjectKernproteine
dc.subjectGentechnisch veränderte Tiere
dc.subjectGentechnologie
dc.subjectHomologe Rekombination
dc.subjectZelldifferenzierung
dc.subjectT-Zelle
dc.subject.ddc570 Biowissenschaften, Biologie
dc.titleUnderstanding the role of SATB1 in CD4+ T cells by analysis of conditionally targeted mice generated by genetic engineering
dc.typeDissertation oder Habilitation
dc.publisher.nameUniversitäts- und Landesbibliothek Bonn
dc.publisher.locationBonn
dc.rights.accessRightsopenAccess
dc.identifier.urnhttps://nbn-resolving.org/urn:nbn:de:hbz:5n-52778
ulbbn.pubtypeErstveröffentlichung
ulbbnediss.affiliation.nameRheinische Friedrich-Wilhelms-Universität Bonn
ulbbnediss.affiliation.locationBonn
ulbbnediss.thesis.levelDissertation
ulbbnediss.dissID5277
ulbbnediss.date.accepted09.11.2018
ulbbnediss.instituteMathematisch-Naturwissenschaftliche Fakultät : Fachgruppe Molekulare Biomedizin / Life & Medical Sciences-Institut (LIMES)
ulbbnediss.fakultaetMathematisch-Naturwissenschaftliche Fakultät
dc.contributor.coRefereeSchultze, Joachim L.


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