Sommer, Daniel: Understanding the role of SATB1 in CD4+ T cells by analysis of conditionally targeted mice generated by genetic engineering. - Bonn, 2018. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc:
author = {{Daniel Sommer}},
title = {Understanding the role of SATB1 in CD4+ T cells by analysis of conditionally targeted mice generated by genetic engineering},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2018,
month = dec,

note = {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.},

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