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Publication : WT-1 is required for early kidney development.

First Author  Kreidberg JA Year  1993
Journal  Cell Volume  74
Issue  4 Pages  679-91
PubMed ID  8395349 Mgi Jnum  J:14317
Mgi Id  MGI:62488 Doi  10.1016/0092-8674(93)90515-r
Citation  Kreidberg JA, et al. (1993) WT-1 is required for early kidney development. Cell 74(4):679-91
abstractText  In humans, germline mutations of the WT-1 tumor suppressor gene are associated with both Wilms' tumors and urogenital malformations. To develop a model system for the molecular analysis of urogenital development, we introduced a mutation into the murine WT-1 tumor suppressor gene by gene targeting in embryonic stem cells. The mutation resulted in embryonic lethality in homozygotes, and examination of mutant embryos revealed a failure of kidney and gonad development. Specifically, at day 11 of gestation, the cells of the metanephric blastema underwent apoptosis, the ureteric bud failed to grow out from the Wolffian duct, and the inductive events that lead to formation of the metanephric kidney did not occur. In addition, the mutation caused abnormal development of the mesothelium, heart, and lungs. Our results establish a crucial role for WT-1 in early urogenital development.
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