Transcriptomic and epigenetic changes after the phenotypic rescue of a Rett Syndrome mouse model

Dulce Vargas Landin

doi:10.26182/9kh2-8h70

Transcriptomic and epigenetic changes after the phenotypic rescue of a Rett Syndrome mouse model

Dulce Vargas Landin

School of Molecular Sciences

Research output: Thesis › Doctoral Thesis

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Abstract

Rett Syndrome (RTT) is a severe dominant X-linked neurological disorder affecting 1:10,000 females. In -95% of the cases, RTT is caused by deleterious mutations in the Methyl-CpG-binding protein 2 (MeCP2). Development and assessment of RTT treatments have been increased since the finding that the rescue of MeCP2 function can restore RTT phenotype in mouse models. Here, I present the transcriptional analysis at single-nucleus resolution coupled with tissue-level DNA methylation profiles of a phenotypically rescued RTT mouse model. Results suggest that neurodevelopmental damage may not be restored in symptomatic and aged individuals, in which supplementary treatments might need to be considered.

Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	The University of Western Australia
Supervisors/Advisors	Lister, Ryan, Supervisor Small, Ian, Supervisor de Mendoza Soler, Alex, Supervisor
Thesis sponsors	Clinical Research Training Program
Award date	12 Apr 2021
DOIs	https://doi.org/10.26182/9kh2-8h70
Publication status	Unpublished - 2021

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10.26182/9kh2-8h70

THESIS - DOCTOR OF PHILOSOPHY - VARGAS LANDIN, Dulce Beatriz - 2021
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Cite this

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title = "Transcriptomic and epigenetic changes after the phenotypic rescue of a Rett Syndrome mouse model",

abstract = "Rett Syndrome (RTT) is a severe dominant X-linked neurological disorder affecting 1:10,000 females. In -95% of the cases, RTT is caused by deleterious mutations in the Methyl-CpG-binding protein 2 (MeCP2). Development and assessment of RTT treatments have been increased since the finding that the rescue of MeCP2 function can restore RTT phenotype in mouse models. Here, I present the transcriptional analysis at single-nucleus resolution coupled with tissue-level DNA methylation profiles of a phenotypically rescued RTT mouse model. Results suggest that neurodevelopmental damage may not be restored in symptomatic and aged individuals, in which supplementary treatments might need to be considered. ",

keywords = "Rett syndrome, phenotypic rescue, MECP2, neurodevelopmental, single nucleus RNA-seq, epigenomics, DNA Methylation, Transcriptomics",

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year = "2021",

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AU - Vargas Landin, Dulce

PY - 2021

Y1 - 2021

N2 - Rett Syndrome (RTT) is a severe dominant X-linked neurological disorder affecting 1:10,000 females. In -95% of the cases, RTT is caused by deleterious mutations in the Methyl-CpG-binding protein 2 (MeCP2). Development and assessment of RTT treatments have been increased since the finding that the rescue of MeCP2 function can restore RTT phenotype in mouse models. Here, I present the transcriptional analysis at single-nucleus resolution coupled with tissue-level DNA methylation profiles of a phenotypically rescued RTT mouse model. Results suggest that neurodevelopmental damage may not be restored in symptomatic and aged individuals, in which supplementary treatments might need to be considered.

AB - Rett Syndrome (RTT) is a severe dominant X-linked neurological disorder affecting 1:10,000 females. In -95% of the cases, RTT is caused by deleterious mutations in the Methyl-CpG-binding protein 2 (MeCP2). Development and assessment of RTT treatments have been increased since the finding that the rescue of MeCP2 function can restore RTT phenotype in mouse models. Here, I present the transcriptional analysis at single-nucleus resolution coupled with tissue-level DNA methylation profiles of a phenotypically rescued RTT mouse model. Results suggest that neurodevelopmental damage may not be restored in symptomatic and aged individuals, in which supplementary treatments might need to be considered.

KW - Rett syndrome

KW - phenotypic rescue

KW - MECP2

KW - neurodevelopmental

KW - single nucleus RNA-seq

KW - epigenomics

KW - DNA Methylation

KW - Transcriptomics

U2 - 10.26182/9kh2-8h70

DO - 10.26182/9kh2-8h70

M3 - Doctoral Thesis

ER -

Transcriptomic and epigenetic changes after the phenotypic rescue of a Rett Syndrome mouse model

Abstract

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