Metabolic alterations in a murine model of Barth syndrome

Laprano, Nicola (2018) Metabolic alterations in a murine model of Barth syndrome. PhD thesis, University of Glasgow.

Abstract

Barth syndrome (BTHS) is a rare monogenic disease characterized by cardiomyopathy, skeletal myopathy and neutropenia, caused by mutations in the Xq28 locus. Mutations in the locus result in the loss of function of the Tafazzin protein (Taz), a transacylase responsible for the final step in the production of mature cardiolipin (CL). CL is a fundamental component of the inner mitochondrial membrane, where it cooperates in the maintenance of membrane stability and in various cellular processes such as mitochondrial respiration, autophagy and reactive oxygen species sensing.
Using a novel murine model of BTHS, we investigated the mitochondrial phenotype, the metabolic signature and the gene expression profile in the heart of Taz knockout (KO) mice.
We identified extensive heart-specific changes in the structure and composition of the mitochondria accompanied by alterations of the metabolome and gene expression. The alterations are specific to the adult, so probably derive from a developmental process happening after birth. The alteration of the gene expression seems to indicate activation of the unfolded protein response, suggesting an effect of stress response pathways in the cellular processes which underlie Barth syndrome.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Mouse models, barth syndrome, transgenics, metabolism, heart disease.
• Subjects: Q Science > Q Science (General)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: Strathdee, Dr. Douglas
• Date of Award: 2018
• Depositing User: Mr Nicola Laprano
• Unique ID: glathesis:2018-9105
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 22 May 2018 15:12
• Last Modified: 14 Feb 2024 09:57
• Thesis DOI: 10.5525/gla.thesis.9105
• URI: https://theses.gla.ac.uk/id/eprint/9105