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Studies on the expression and function of p56Lck and core binding factor during thymocyte development

Buckland, Jennifer Ruth; (2000) Studies on the expression and function of p56Lck and core binding factor during thymocyte development. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Haematopoiesis, the generation of mature blood cells, is controlled by signals that activate lineage specific genes, allowing for cellular proliferation, survival and differentiation. This study focuses on the regulation and function of genes coding for molecules specifically involved in T cell development. The first gene investigated was the gene coding for the lymphoid-specific, Src-family protein tyrosine kinase, p56Lck that was first discovered as being over-expressed in a lymphoma cell line. This kinase has been shown to play a vital role in thymocyte differentiation. The timing of p56Lck expression during thymocyte development was determined. The results show that the expression of the p56Lck gene is developmentally regulated at the post-transcriptional level at the precise stage at which its upstream receptor complex, the pre-TCR, is expressed. In addition, transgenic mice expressing green fluorescent protein (GFP) under the control of the p56Lck proximal promoter were generated and analysed. The implications of these results for future use of this promoter are discussed. Secondly, the role of Core Binding Factor (CBF), a heterodimeric transcription factor consisting of an α and a β subunit, in thymocyte development was investigated. Translocations targeting the CBFα2 and CBFβ genes are amongst the most frequent mutations in human leukaemia. The a subunits contain a conserved DNA binding RUNT domain, via which these CBF proteins bind to sequences in a variety of T cell specific genes. CBFα2 and CBFβ deficient mice have been generated but their early lethality precludes the study of T cell differentiation in these mice. CBF dominant negative transgenic mice were generated in order to investigate the role of these transcription factors in thymocyte development. Preliminary analysis of these mice has revealed a potential role for CBF in the regulation of thymocyte survival.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Studies on the expression and function of p56Lck and core binding factor during thymocyte development
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences; T cell development
URI: https://discovery.ucl.ac.uk/id/eprint/10111623
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