Morgan, RS
(2019)
Understanding the role of HACD enzymes and very long chain fatty acids in muscle development and disease
PhD thesis, University of Liverpool.
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Abstract
3-hydroxyacyl-coA dehydratase (HACD) enzymes form part of a complex that elongates fatty acids with very long carbon chain length (VLCFA) (>20C). There are four paralogous HACD enzymes in mammals (encoded by HACD1-4), each with a distinct tissue distribution: HACD1 is specifically expressed in striated muscles and mutations in HACD1 cause congenital myopathies in humans, dogs and mice. The canine autosomal recessive centronuclear myopathy, HACD1-CNM, is the most prevalent neuromuscular disorder in dogs with 15-20% of the Labrador retriever breed carrying the causative mutation. The pathogenesis of HACD1-associated myopathies and the roles of VLCFA in developing and mature muscle remain poorly understood. Membranous abnormalities, particularly affecting excitation-contraction coupling apparatus at the triad, are an important feature of CNMs due to other genetic causes and progressive t-tubule disorganisation has recently been documented in CNM affected dogs. We hypothesised that HACD1-deficiency reduces levels of specific VLCFA and impacts upon normal triad structure and function. We further hypothesised that hacd1-mutant zebrafish embryos can be used to model HACD1-associated myopathies. I aimed to: characterise ... (continues)
| Item Type: | Thesis (PhD) |
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| Divisions: | Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 06 Jan 2020 14:02 |
| Last Modified: | 28 Oct 2024 18:55 |
| DOI: | 10.17638/03057583 |
| Supervisors: |
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| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3057583 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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