Investigating lung function gene GSTCD using gene targeting in human and mouse systems

Respiratory diseases are a significant global health concern and burden, with one of the major respiratory diseases causing a decline in lung function being chronic obstructive pulmonary disease (COPD). Critically, current therapies have limited impact. Recently, single nucleotide polymorphisms at c...

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Main Author: Probert, Kelly
Format: Thesis (University of Nottingham only)
Language:English
Published: 2016
Subjects:
Online Access:https://eprints.nottingham.ac.uk/33199/
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author Probert, Kelly
author_facet Probert, Kelly
author_sort Probert, Kelly
building Nottingham Research Data Repository
collection Online Access
description Respiratory diseases are a significant global health concern and burden, with one of the major respiratory diseases causing a decline in lung function being chronic obstructive pulmonary disease (COPD). Critically, current therapies have limited impact. Recently, single nucleotide polymorphisms at chromosome locus 4q24 have been identified as associated with the lung function measure forced expiratory volume in 1 second and COPD, specifically identifying the gene Glutathione S-transferase C-terminal domain containing (GSTCD) as a viable candidate gene. Data indicate that GSTCD or associated biological pathways may be a potential target for interventions to alleviate COPD. Further analysis into the pathways and phenotypic effects of this gene may aid our understanding of the mechanisms by which GSTCD is associated with and influences lung function and COPD. Importantly, there are currently no reports describing the function of GSTCD, therefore this project aimed to understand the consequences of reduction and loss of GSTCD within the context of lung biology. This was performed by analysis of human cell knock-down and knock-out mouse models respectively, as well as utilising established protein sequence homology analysis to infer potential function. Conclusions drawn from these results suggest a possible role for GSTCD in cell growth in a human in vitro GSTCD knock-down model, but no gross morphological differences were evident in Gstcd knock-out mice. Additionally, GSTCD sequence homology analysis in several protein prediction servers suggests methyltransferase activity as a potential function for GSTCD, differing from the initial prediction of glutathione S-transferase enzyme activity. Overall, this research represents an important and novel development for the lung function and COPD associated gene GSTCD, providing interesting avenues for future exploration.
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spelling nottingham-331992025-02-28T13:26:51Z https://eprints.nottingham.ac.uk/33199/ Investigating lung function gene GSTCD using gene targeting in human and mouse systems Probert, Kelly Respiratory diseases are a significant global health concern and burden, with one of the major respiratory diseases causing a decline in lung function being chronic obstructive pulmonary disease (COPD). Critically, current therapies have limited impact. Recently, single nucleotide polymorphisms at chromosome locus 4q24 have been identified as associated with the lung function measure forced expiratory volume in 1 second and COPD, specifically identifying the gene Glutathione S-transferase C-terminal domain containing (GSTCD) as a viable candidate gene. Data indicate that GSTCD or associated biological pathways may be a potential target for interventions to alleviate COPD. Further analysis into the pathways and phenotypic effects of this gene may aid our understanding of the mechanisms by which GSTCD is associated with and influences lung function and COPD. Importantly, there are currently no reports describing the function of GSTCD, therefore this project aimed to understand the consequences of reduction and loss of GSTCD within the context of lung biology. This was performed by analysis of human cell knock-down and knock-out mouse models respectively, as well as utilising established protein sequence homology analysis to infer potential function. Conclusions drawn from these results suggest a possible role for GSTCD in cell growth in a human in vitro GSTCD knock-down model, but no gross morphological differences were evident in Gstcd knock-out mice. Additionally, GSTCD sequence homology analysis in several protein prediction servers suggests methyltransferase activity as a potential function for GSTCD, differing from the initial prediction of glutathione S-transferase enzyme activity. Overall, this research represents an important and novel development for the lung function and COPD associated gene GSTCD, providing interesting avenues for future exploration. 2016-07-19 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/33199/1/Kelly%20Probert%20MPhil%20Thesis%20-%20Final.pdf Probert, Kelly (2016) Investigating lung function gene GSTCD using gene targeting in human and mouse systems. MPhil thesis, University of Nottingham. Glutathione S-transferase C-terminal domain Chronic obstructive pulmonary disease Lung function
spellingShingle Glutathione S-transferase C-terminal domain
Chronic obstructive pulmonary disease
Lung function
Probert, Kelly
Investigating lung function gene GSTCD using gene targeting in human and mouse systems
title Investigating lung function gene GSTCD using gene targeting in human and mouse systems
title_full Investigating lung function gene GSTCD using gene targeting in human and mouse systems
title_fullStr Investigating lung function gene GSTCD using gene targeting in human and mouse systems
title_full_unstemmed Investigating lung function gene GSTCD using gene targeting in human and mouse systems
title_short Investigating lung function gene GSTCD using gene targeting in human and mouse systems
title_sort investigating lung function gene gstcd using gene targeting in human and mouse systems
topic Glutathione S-transferase C-terminal domain
Chronic obstructive pulmonary disease
Lung function
url https://eprints.nottingham.ac.uk/33199/