Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Biochemistry

Supervisor

Dr. Nathalie Berube

Abstract

Astrocytes perform many homeostatic roles in the brain while supplying metabolites to neurons and mediating synaptic transmission. The current study explored a possible role of the Atrx gene in astrocytes. Hypomorphic mutations in this gene cause the ATR-X intellectual disability syndrome. Deletion of Atrx in the forebrain leads to an apparent increase in reactive astrocytes, potentially caused by the high level of neuroprogenitor cell death. To avoid such non cell-autonomous effects on astrocytes, we generated mice with inducible conditional inactivation of Atrx in astrocytes. Preliminary analysis two weeks following induction of Atrx gene deletion revealed variably lower expression of Connexin 30 (Gjb6), encoding a gap junction protein. Morphologically, ATRX-null astrocytes displayed larger domain coverage by peripheral astrocytic processes, suggesting altered functionality. This work provides key advances to our understanding of ATRX function in astrocytes and provides a unique mouse model for future investigations.

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