Lowe, Kate (2011)
M.Res. thesis, University of Birmingham.
Project 1: The platelet C type lectin-like type II (CLEC-2) transmembrane receptor has been shown to interact with its endogenous ligand, podoplanin, on lymphatic endothelium and mediate separation from blood vessels. Here, conditional deletion of CLEC-2 or a mutation in signalling molecule Syk, specifically in the megakaryocyte/platelet lineage, was seen to cause a severe blood-lymphatic mixing phenotype. As constitutive loss of CLEC-2 in mice is lethal at birth, radiation chimeras have been pivotal to investigating the role of CLEC-2 in platelet function. This pilot study was conducted to investigate the role of platelets in the recovery from radiation injury. Mice were subjected to irradiation and reconstituted with CLEC-2+/+ or CLEC-2-/- foetal liver cells. Immunofluorescence in the intestinal mesentery at 9 days showed disrupted vasculature in CLEC-2-/- mice. The only visible difference between the two sets of chimeras was blood in the intestine of CLEC-2-/- mice at 28 days. Terminal deoxynucleotidyl end labeling (TUNEL) showed no difference in the percentage of apoptotic cells in the livers of CLEC-2+/+ and CLEC-2-/- mice but an increase in the spleen. These results support the idea of a progressive intestinal phenotype and support a role for CLEC-2 and Syk in the separation and organization of blood and lymphatic vessels.
|Type of Work:||M.Res. thesis.|
|Supervisor(s):||Watson, Steve P. and Finney, Brenda and Madhani, Melanie|
|School/Faculty:||Colleges (2008 onwards) > College of Medical & Dental Sciences|
|Department:||Centre for Cardiovascular Sciences, Institute of Biomedical Research, College of Medical and Dental Services|
RC Internal medicine
|Institution:||University of Birmingham|
|Library Catalogue:||Check for printed version of this thesis|
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