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Genetic analysis of murine tissue repair and inflammation

Cooper, Lisa Deanne; (2003) Genetic analysis of murine tissue repair and inflammation. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Studies in recent years have revealed much about the cell biology of wound repair but the current understanding of the genetic regulation and coordination of the various processes that underlie repair is relatively poor. Concomitant with the repair response is an inflammatory response previously thought to be an essential driver of many events of repair. One consequence of the inflammatory response is thought to be connective tissue fibrosis, or scarring. Clues to the genetic basis of repair and inflammation and the fibrotic response are essential for the design of therapeutic targets for improving wound repair in the clinic. In this thesis, I have attempted to dissect the genetics of repair and its associated inflammatory response using the "macrophageless" PU.1 null neonatal mouse. The PU.1 transcription factor is essential for the differentiation of several haematopoetic lineages. Mice null for PU.1 cannot raise an inflammatory response at the wound site, yet undergo perfect scar-free repair. Using Affymetrix microarrays, I have identified genes differentially expressed at the wound site of the PU.1 null mouse and its wild type sibling. Cluster analysis of the temporal profiles of wound-induced genes, identifies four clusters of repair genes, expressed similarly in the presence and absence of inflammation and corresponding to physiologically significant episodes in repair. I have also identified three clusters of genes induced at the wild type wound coincident with the inflammatory response, but whose expression is absent or whose patterns of expression are dramatically different in the PU.1 null mouse, where there is no inflammatory response. By in situ hybridisation, I have investigated the spatial profiles of genes from each of the repair and inflammation clusters. Clearly it is important to determine the function of these wound-induced genes and I have carried out a preliminary study of the live analysis of gene function using a model of epithelial repair in the Drosophila embryo.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Genetic analysis of murine tissue repair and inflammation
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Wound repair
URI: https://discovery.ucl.ac.uk/id/eprint/10098646
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