Supplementary materials for PhD thesis 'Genetic and developmental interactions between the genes encoding Wilms tumour 1 (Wt1) and β-catenin (Ctnnb1)'

<p dir="ltr"><i>This dataset comprises the files contained on a CD-ROM which was attached to the thesis when it was submitted in 2010. It was uploaded to ORDO in 2025 for preservation purposes. For more information, please refer to the thesis </i><a href="https://oro.open.ac.uk/63683/" rel="noreferrer" target="_blank">Genetic and developmental interactions between the genes encoding Wilms tumour 1 (Wt1) and β-catenin (Ctnnb1)</a><i> via ORO</i><i>.</i></p><p dir="ltr">Wilms’ tumour is a childhood kidney cancer which results from misdevelopment of the kidney. Inactivating mutations in the <i>WT1</i> tumour suppresor gene are responsible for 15-20 % of cases. This subset of Wilms’ tumour was also shown to be strongly associated with activating mutations in β-catenin. In contrast to most types of cancer where the mutation is found in any of four phosphorylation sites on β-catenin, Wilms tumours show a clear preferential selection for a Ser45 mutation, accounting for 90% of the tumours. Based on this, we hypothesize that there are fundamental differences between the effects of different β-catenin mutations, challanging the prevailing dogma. In order to test this hypothesis, I generated an inducible β-catenin allelic series in ES cells and generated mice from these cells. Both expression of endogenous β-catenin target genes in ES cells and in vivo analysis of mice homozygous for these activated β-catenin mutant alleles revealed differences, supporting our hypothesis. As both Wt1 and β-catenin are essential in normal kidney development, and found mutated in the same tumour samples, I analysed the effect of activating mutations of β-catenin on <i>Wt1</i>- deficient background kidneys. Surprisingly, a partial rescue of the <i>Wt1</i>-deficient phenotype was shown in 3 day organ culture and in E l8.5 kidney sections and confirmed by marker analysis via Real Time PCR. The implications of these findings for development, tumour biology and signalling pathways are discussed.</p>