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Experimental emphysema in the blotchy mouse. A morphometric study using image analysis

McCartney, Alison Caroline Elliot; (1993) Experimental emphysema in the blotchy mouse. A morphometric study using image analysis. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

Smoking remains the major aetiological factor in emphysema but it is paradoxical that most smokers do not appear to develop the disease. Inheritable abnormalities in lung scleroproteins may underlie a propensity to develop emphysema. This hypothesis was tested in two animal models. Experiments were first performed on an animal model, the Wistar rat, which does not exhibit any genetically determined lung disease. Instillation of elastase and saline caused increase in airspace transects in the rat. A sensitive and rapid morphological technique was used to evaluate the light microscopic appearances of the induced lung disease. The second model was the blotchy mouse, which has an X- linked deficiency of lysyl oxidase, leading to faulty cross linkage of elastin. [Hemizygous male animals have abnormal lungs, aortic aneurysms and curly whiskers.] This thesis documents the effects on the lungs of increasing age and manipulation of the elastase- antielastase balance in all phenotypes and genotypes of these mice, which were established as the first outbred colony in the U.K. Scanning electron microscopy was performed on the blotchy mice and their sibling controls. In the blotchy mice statistically significant differences in airspace transects were demonstrable in the untreated hemizygous and homozygous mice compared to control mice. The heterozygous female mice showed the effects of lyonisation of the gene, their lung transects lying in a band between those of the hemi or homozygous animals compared to controls. Animals with mild or severe damage remained vulnerable to instilled elastase, showing that it is possible to augment genetically determined lung disease although the effects due aging alone were greatest in the control animals. The biochemical results suggest that the interdependence and plasticity of lung structural proteins other than elastin are also important factors in the regulation and expression of both induced and naturally occurring disease.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Experimental emphysema in the blotchy mouse. A morphometric study using image analysis
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10100030
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