Régulation de l'expression des facteurs de transcription MEF2 dans les cellules de Leydig et développement d'outils pour l'étude de leur rôle dans un modèle de souris
|Advisor:||Tremblay, Jacques J.|
|Abstract:||Functional Leydig cells are indispensable for spermatogenesis and for the development and maintenance of a male phenotype. Proper development of Leydig cells depends on specific gene expression. Gene expression is finely regulated by different transcription factors. In Leydig cells, we have identified 3 of the 4 MEF2 transcription factors (MEF2A, 2C and 2D).Their role in these cells remains to be fully characterized. Considering that these factors are indispensable for the development and function of other tissues, we propose that MEF2 factors play similar roles in the development and function of Leydig cells. Transcriptomic analysis of MEF2-deficient Leydig cells revealed several down regulated genes. An in vitro study of the activity of a promoter for one of those genes, Bmal1, allowed the study of the implication of MEF2 in the expression of that gene. The regulation of MEF2 expression and activation in response to different treatments of Leydig cells in culture was also studied. The mRNA and protein levels for MEF2 factors were quantified following various treatments. Preliminary results indicated that MEF2 levels are not affected by these treatments. Another aspect of the project was to develop an approach that would eventually be used to study the roles of MEF2 transcription factors in Leydig cell development and function in a mouse model. Since three MEF2 transcription factors are present in Leydig cells, a conventional knockout approach of all three genes simultaneously was difficultly achievable. Therefore, we chose an inducible, conditional, active dominant negative MEF2 model, in order to allow us to establish the importance of MEF2 factors in Leydig cells. Preliminary results obtained during validation in a Leydig cell line support the usefulness of this approach.|
|Document Type:||Mémoire de maîtrise|
|Open Access Date:||13 September 2021|
|Collection:||Thèses et mémoires|
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