Show simple item record

dc.contributor.advisorBaird, Margaret
dc.contributor.advisorBraithwaite, Antony
dc.contributor.advisorSlatter, Tania
dc.contributor.authorRoth, Imogen Margaret
dc.date.available2011-12-20T22:53:43Z
dc.date.copyright2011
dc.identifier.citationRoth, I. M. (2011). The role of Δ122p53 in B cell development (Thesis, Bachelor of Biomedical Sciences with Honours). University of Otago. Retrieved from http://hdl.handle.net/10523/2079en
dc.identifier.urihttp://hdl.handle.net/10523/2079
dc.description.abstractp53 is a crucial tumour suppressor, as evidenced by three important observations: p53 is lost or mutated in half of all human cancers, an inheritable p53 mutation predisposes to an early onset of multiple cancer types, and mice which lack p53 entirely all develop cancer. p53 is thus the ‘guardian of the genome’ (Lane, 1992), and prevents tumourigenesis by inducing the transcription of genes that carry out cell cycle arrest, apoptosis, DNA repair, and cellular senescence. p53 is normally present as a number of isoforms in healthy tissue, though some, including Δ133p53, are elevated in some cancer types. A mouse model of the Δ133p53 isoform, Δ122p53, has been shown to act as an oncogene and have a pro-inflammatory profile. Δ122p53 mice also have a distinctive B cell tumour spectrum largely composed of diffuse large B cell lymphomas, which was the starting point of this research project. The aims of this project were to elucidate the fundamental phenotypic differences between wild type and Δ122p53 mice, largely focusing on differences in cell surface marker expression. We also sought to determine the differences between wild type and Δ122p53 mice in their basal cell cycle profiles and p53-mediated response to DNA damage. In addition, we attempted to follow these differences as the mice aged to determine the potential onset of tumourigenesis in Δ122p53 mice. The results of this project show that Δ122p53 mice have a greater spleen mass than wild type mice, and the bone marrow and spleen have an elevated G2/M population and undergo less apoptosis than wild type mice. While none of the cell surface markers showed consistent differences in expression between wild type and Δ122p53 mice, there were several Δ122p53 mice that had alterations in the expression of the lineage cocktail and Ig κ light chain markers compared to their age matched wild types. The results of an earlier study were replicated, showing that Δ122p53 mice have elevated levels of serum IL-6, a cytokine implicated in many cancer types including those commonly found in Δ122p53 mice. This project also showed a reduction in serum IgG and IgM levels in Δ122p53 mice, suggesting that the Δ122p53 isoform is preventing B cell maturation. This project concludes that the Δ122p53 isoform affects p53 mediated responses and B cell development. We propose that the lineage cocktail and Ig κ light chain markers are potential markers of the tumour precursor population in Δ122p53 mice. Further studies are needed to confirm this, which we anticipate will demonstrate the role of the Δ122p53 isoform in B cell development. This will provide insight into an oncogenic p53 isoform in mice, closely related to the Δ133p53 isoform found in humans, and may provide clues to potential cancer therapies.en_NZ
dc.language.isoenen_NZ
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectp53 antioncogeneen_NZ
dc.subjectp53 isoformen_NZ
dc.subjectΔ122p53en_NZ
dc.subjectB cell developmenten_NZ
dc.titleThe role of Δ122p53 in B cell developmenten_NZ
dc.typeThesis
dc.date.updated2011-12-20T01:51:50Z
dc.language.rfc3066en
thesis.degree.disciplineMicrobiology and Immunologyen_NZ
thesis.degree.nameBachelor of Biomedical Sciences with Honoursen_NZ
thesis.degree.grantorUniversity of Otago
thesis.degree.levelHonours
otago.interloanno
otago.openaccessAbstract Only
 Find in your library

Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item is not available in full-text via OUR Archive.

If you are the author of this item, please contact us if you wish to discuss making the full text publicly available.

This item appears in the following Collection(s)

Show simple item record