Year: 2020
Type: dissertation
Abstract: Rett Syndrome (RTT) is a neurodevelopmental disorder in girls with mutations in the X-linked gene that encodes methyl-CpG-binding protein 2 (MECP2). Using neurons differentiated from patient-derived induced pluripotent stem cells (iPSC), I analyzed the MECP2 RNA levels, MECP2 protein levels, morphology, and extracellular electrophysiology of a novel L124W MECP2 mutation. My results show that L124W exhibits no change in RNA, protein, dendrite length, soma size, or electrophysiology but does show a subtle significant change in dendrite order and dendrite complexity. This is the first in vitro iPSC characterization of a mild RTT case. While developing a CRISPR/Cas9 protocol that will eventually genetically rescue the L124W mutation, I also generated the first iPSC knock-out lines for NEDD4L, a downstream target of MECP2. Overall, this work can be used to further elucidate MECP2 pathways and eventually identify treatments for RTT.
Source: TSpace (University of Toronto)
Author: Leah C. DeJong
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3133414228