Understanding the role of SATB1 in CD4+ T cells by analysis of conditionally targeted mice generated by genetic engineering
Understanding the role of SATB1 in CD4+ T cells by analysis of conditionally targeted mice generated by genetic engineering
dc.contributor.advisor | Beyer, Marc | |
dc.contributor.author | Sommer, Daniel | |
dc.date.accessioned | 2020-04-25T13:42:58Z | |
dc.date.available | 2020-04-25T13:42:58Z | |
dc.date.issued | 12.12.2018 | |
dc.identifier.uri | https://hdl.handle.net/20.500.11811/7677 | |
dc.description.abstract | Special-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.iso | eng | |
dc.rights | In Copyright | |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | Immunsystem | |
dc.subject | Kernproteine | |
dc.subject | Gentechnisch veränderte Tiere | |
dc.subject | Gentechnologie | |
dc.subject | Homologe Rekombination | |
dc.subject | Zelldifferenzierung | |
dc.subject | T-Zelle | |
dc.subject.ddc | 570 Biowissenschaften, Biologie | |
dc.title | Understanding the role of SATB1 in CD4+ T cells by analysis of conditionally targeted mice generated by genetic engineering | |
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-52778 | |
ulbbn.pubtype | Erstveröffentlichung | |
ulbbnediss.affiliation.name | Rheinische Friedrich-Wilhelms-Universität Bonn | |
ulbbnediss.affiliation.location | Bonn | |
ulbbnediss.thesis.level | Dissertation | |
ulbbnediss.dissID | 5277 | |
ulbbnediss.date.accepted | 09.11.2018 | |
ulbbnediss.institute | Mathematisch-Naturwissenschaftliche Fakultät : Fachgruppe Molekulare Biomedizin / Life & Medical Sciences-Institut (LIMES) | |
ulbbnediss.fakultaet | Mathematisch-Naturwissenschaftliche Fakultät | |
dc.contributor.coReferee | Schultze, Joachim L. |
Files in this item
This item appears in the following Collection(s)
-
E-Dissertationen (4057)