Recently, a population of embryonic thymic epithelial cells has been isolated in the mouse, identified by the monoclonal antibodies MTS20 and MTS24, which can differentiate into all thymic epithelial cell types and is sufficient to generate a functional thymus in vivo. This strongly suggests that a common, MTS20<sup>+</sup>24<sup>+</sup> progenitor gives rise to all mature sub-populations of TEC, and opens up the possibility of supporting thymopoiesis in vitro using a single TEPC line. The aim of this thesis was therefore to generate cell lines of TEPC’s that retain the capacity to differentiate and form a functional thymic microenvironment. To allow the derivation of cell lines that correspond to the progenitor phenotype, the developmental capacity of TEPC’s must be suspended at a stage prior to the onset of differentiation. However, the developmental block must be reversible, so that the ability to form a functional thymic microenvironment is retained. The differentiation of TEPC’s is dependant on the transcription factor <i>Foxn1, </i>which is expressed specifically in epithelial cells of the thymus and epidermis. Nude mice, which harbour a loss of function mutation in <i>Foxn1, </i>contain an alymphoid thymus consisting of immature, MTS20<sup>+</sup>24<sup>+</sup> epithelial cells. Thus, the TEPC population forms independently of <i>Foxn1, </i>but requires expression of this transcription factor to form a mature thymic microenvironment. This thesis therefore describes the generation of transgenic mice in which <i>Foxn1 </i>expression is reversibly down-regulated. In addition, as a consequence of Foxnl driven SV40TAg expression, these mice also result in the conditional immortalisation of TEC’s. A phenotypic analysis of these mice is described, as is the derivation and characterisation of TEC lines.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:660061 |
| Date | January 2005 |
| Creators | Nowell, Craig Scott |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/15539 |
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