Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.649147
Title: Characterisation of lung disease in mouse models of cystic fibrosis
Author: Davidson, D. J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
Abstract:
Firstly, this thesis describes 1) the development and quantification of methods for the delivery of bacteria to the murine lung and 2) the analysis of the histopathological phenotype of mouse models of CF congenic on a C57B1/6N background, in response to such techniques. These studies were performed using a clinical strain of Staphylococcus aureus, a pathogen that is characteristic of the early stages of lung infection in CF. The experiments addressed the null hypothesis that there was no difference between the histopathological responses of 1) Cftr tm1Hgu/Cftrtm1Hgu mice or 2) Cftrtm1Hgu/Cftrtm1Unc compound heterozygote mice, and non-CF littermates. The results led to the following conclusions; a) mouse models of CF (Cftrtm1Hgu/Cftrtm1Hgu and Cftrtm1Hgu/Cftrtm1Unc) congenic on a C57B1/6N background developed lung pathology in response to repeated exposure to nebulised S. aureus, b) significantly more severe pathology was observed in CF mice compared to non-CF littermate controls, c) the spectrum of disease observed in CF mice and non-CF littermates congenic on a C57B1/6N background was narrowed in comparison to those on an outbred MF1 background, with wild type mice more severely affected, d) No difference was observed between the severity of disease in the Cftrtm1Hgu/Cftrtm1Unc mice in comparison to the Cftrtm1Hgu/Cftrtm1Hgu mice, implying that the reduction in background levels of wild type CFTR did not have a major influence upon the observed response to pathogen exposure, and e) assessment of the histopathology suggested an exaggerated response rather than abnormality in any one aspect of this response. Until recently the mechanisms by which dysfunction of CFTR could lead to the development of characteristic CF lung pathology remained unclear. However, several compelling, and competing, hypotheses have been proposed, based largely on in vitro studies. This thesis describes studies designed to complement the published research by utilising mouse models of CF and address the relevance of several of these theories in this model system.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.649147  DOI: Not available
Share: