期刊
DISEASE MODELS & MECHANISMS
卷 8, 期 8, 页码 903-U271出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dmm.018523
关键词
WT1; Wilms' tumour; Kidney development; Mouse model
资金
- EuReGene
- EU [05085]
- Olson trust
- National Center for Replacement, Refinement and Reduction of Animals in Research [94808]
- Association for International Cancer Research [04-297]
- MRC grant [MR/K010735/1]
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/J004316/1]
- Biotechnology and Biological Sciences Research Council [BBS/E/D/20221657] Funding Source: researchfish
- Medical Research Council [MC_PC_U127527180, MR/M010341/1, MC_PC_U127527203, MR/K010735/1] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/K500549/1] Funding Source: researchfish
- BBSRC [BBS/E/D/20221657] Funding Source: UKRI
- MRC [MR/K010735/1, MC_PC_U127527180, MC_PC_U127527203, MR/M010341/1] Funding Source: UKRI
Wilms' tumours, paediatric kidney cancers, are the archetypal example of tumours caused through the disruption of normal development. The genetically best-defined subgroup of Wilms' tumours is the group caused by biallelic loss of the WT1 tumour suppressor gene. Here, we describe a developmental series of mouse models with conditional loss of Wt1 in different stages of nephron development before and after the mesenchymal-to-epithelial transition (MET). We demonstrate that Wt1 is essential for normal development at all kidney developmental stages under study. Comparison of genome-wide expression data from the mutant mouse models with human tumour material of mutant or wild-type WT1 datasets identified the stage of origin of human WT1-mutant tumours, and emphasizes fundamental differences between the two human tumour groups due to different developmental stages of origin.
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