The role of Δ122p53 in B cell development
Roth, Imogen Margaret
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Roth, 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/10523/2079
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Abstract:
p53 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.
Date:
2011
Advisor:
Baird, Margaret; Braithwaite, Antony; Slatter, Tania
Degree Name:
Bachelor of Biomedical Sciences with Honours
Degree Discipline:
Microbiology and Immunology
Publisher:
University of Otago
Keywords:
p53 antioncogene; p53 isoform; Δ122p53; B cell development
Research Type:
Thesis
Languages:
English
Collections
- Microbiology and Immunology [178]
- Thesis - Honours [339]