Caractérisation d'un modèle murin déplété en la protéine FANCI : phénotypes méiotiques et comportementaux, et résistance aux aldéhydes

Authors: Béliveau Lapointe, Mariline
Advisor: Masson, Jean-Yves
Abstract: Fanconi anemia (FA) is a rare recessive disease associated with a defect in the pathway of DNA double strand breaks repair (FA pathway). These double stranded breaks are caused by crosslinking agents by creating a covalent bond between the two opposite strands and blocking polymerases during DNA replication or transcription. My project’s principal interest is a major protein it this pathway : the FANCI protein. It is described as acting together with FANCD2 protein to recruit DNA repair machinery. We hypothesised that FANCI has an important role in development, in meiosis and that it is implicated in cells’ aldehydes resistance. After the creation of a mouse model depleted in FANCI, with did anxiety and memory behavior tests to deeply characterize our mouse model. Also, results of gonad histologic cuts confirmed mouse sterility. More specifically, we did a meiotic spread and immunofluorescence to see FANCI on meiotic chromosomes. We also treated embryonic fibroblasts with mitomycin C, an exogenous crosslinking agent, and then wanted to check with an endogenous source, like aldehydes, on FANCI depleted human cells. We also observed 53BP1 and γ-H2AX foci formation to check for double strand break accumulation. Behavior tests do not show any significative tendancy. We observe a colocalization between FANCI and the resection marker RPA. Moreover, FANCI depletion gives an aldehyde resistance to cells. 53BP1 and γ-H2AX foci show a population of cells with a very high level of foci and others that have the same amount of foci as the control cells.
Document Type: Mémoire de maîtrise
Issue Date: 2017
Open Access Date: 24 April 2018
Grantor: Université Laval
Collection:Thèses et mémoires

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