Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Developmental Biology

Supervisor

Dr. Nathalie Berube

Abstract

ATRX is a chromatin remodeling protein important for neural development, and ATRX inactivation leads to genomic instability, mitotic defects and TP53-mediated apoptosis. In the last few years, ATRX mutations were identified in a large proportion of paediatric and adult gliomas that often coincide with mutations in the tumor suppressor TP53. The present work shows that combinatorial loss of ATRX and TP53 function in vitro causes genomic instability while improving cell viability, identifying potential early events in gliomagenesis. Furthermore, several gene transcripts associated with glioma development and known oncogenic pathways were significantly upregulated in the Atrx-null neonatal mouse forebrain. Finally, a mouse model of Atrx and Tp53 deficiency in the mouse CNS was generated, providing a tool for future investigations.


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