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Title: The characterisation of the murine gene for properdin
Authors: Dupont, Lynda.
Award date: 2000
Presented at: University of Leicester
Abstract: The three pathways of complement activation lead to the proteolysis of the same component, C3, that will then carry on the enzymatic cascade of the downstream components and the MAC proteins.;In the context of the alternative pathway, the enzyme responsible for the proteolysis of C3 relies upon properdin, a six thrombospondin repeat domains protein, for its stability and activity. Thus properdin has a key role in ensuring the full activity of the alternative pathway.;Cases studies of properdin deficiency show that the patients have a higher risk to suffer recurrent bacterial infections, in particular of meningococcal nature, and that the ensuing level of mortality is also higher than non-deficient patients.;The work described in this thesis is the characterisation of the murine gene for properdin. High homology between humans and mice of the complement activation, regulation and components, makes these animals a privileged laboratory model. The mouse properdin gene was isolated by screening a mouse genomic library of the SVJ129 strain and sequence analysis of phage clones determined to represent the genomic sequence for properdin. The properdin gene was determined to contain 9 exons encoding for the leader peptide, N-terminus, the six thrombospondin repeats and the 3' untranslated region. Each thrombospondin repeat was shown to be encoded by a single exon with the exception of the sixth repeat which is encoded by two separate exons interrupted by an intronic sequence. The sequencing of the gene confirmed the homology to human properdin at the genomic level, thus validating further the value of the mouse model to study properdin deficiency. The characterisation of the mouse gene for properdin will allow the generation of a mouse strain deficient for the properdin gene to study the phenotype of these transgenic animals.
Type: Thesis
Level: Doctoral
Qualification: PhD
Rights: Copyright © the author. All rights reserved.
Appears in Collections:Theses, Dept. of Biology
Leicester Theses

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