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Title: Transgenic analysis of the Wilms' tumour 1 gene (WT1) expression and regulation
Author: Moore, Adrian W.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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Investigation of a locus, at 11p13, predisposing to Wilms' tumour led to the identification of the Wilms' tumour suppressor gene, (WT1). I used a transgenic approach to examine aspects of both WT1 expression and regulation, A 5 kb region (USWT1) of the putative WT1promoter was linked to a lacZ reporter and used to generate several transgenic embryos. The expression pattern driven by this reporter construct was similar to that of the endogenous locus but very weak and susceptible to position effects. To overcome this problem a YAC spanning the human WT1 locus was used to drive expression of a lacZ reporter in transgenic mouse embryos. The reporter gene expression driven by this construct mirrors that of the endogenous Wt1 locus except in the sex specific Sertoli and granulosa cells. I used the YAC driven reporter gene expression in these transgenic embryos to carefully study the expression pattern of Wt1. The transgene is expressed in both mesodermal and neuro-ectodermal lineages. It is expressed in mesenchymal cells produced by the proliferating coelomic epithelium; hence Wt1 is a marker for this specific cell type. It is also expressed in the interdigtal mesenchyme during limb morphogenesis. This newly identified site of Wt1 expression was confirmed by Wt1 mRNA in situ analysis and raises a potential role for Wt1 in the control of apoptosis. Cells expressing the transgene are present in all the differentiating epaxial musculature of the embryo implying that Wt1 may play a role in myogenesis. In the neuro-ectodermal lineage, transgene expression implies that Wt1 may play a role in neural patterning. The YAC transgene expression studies presented in this thesis complement further YAC transgenic work we have undertaken. Trangenic animals were made with an unmodified YAC spanning the WT1 locus. This transgene was able to partially rescue the Wt1 homozygous null phenotype when crossed onto the Wt1 knockout background.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available