| WT1 is a modifier of the Pax2 mutant phenotype: cooperation and interaction between WT1 and Pax2. | |
| | |
MedLine Citation:
|
PMID: 14603255 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Metanephric kidney development requires an inductive interaction between the ureteric bud and progenitor mesenchyme, where the early expression of two genes, Wilms' tumour 1 (WT1) and paired box 2 (Pax2), establishes critical but unknown developmental pathways. Indeed, transgenic mice with deregulated overexpression of Pax2 exhibit structural kidney defects and impaired renal function, as do mice harboring targeted disruptions and/or spontaneous mutations of either the Pax2 or WT1 genes. WT1 and Pax2 are thought to regulate each other's expression during renal development. To better define the relationship between WT1 and Pax2, we generated mouse embryos containing heterozygous mutations in both genes. WT1(+/-)/Pax2(1Neu/+) kidneys were 50% smaller than wild-type kidneys. They were characterized by severe attenuation of the renal medulla, and reduced development of calyces and the renal pelvis. Renal cortex development in compound heterozygotes culminated in fewer nephrons than in WT1(+/-), Pax2(1Neu/+) or wild-type mice. Only minor variations in the mesenchymal expression pattern of Pax2 protein, and the mRNA expression levels of Pax2 and WT1, were noted in mutant kidneys. We show that WT1 and Pax2 proteins interact in vitro and in vivo, demonstrating that WT1 and Pax2 can form a molecular complex. Our data suggest that WT1 is a modifier of the Pax2 mutant phenotype. |
| | |
Authors:
|
Maria Teresa Discenza; Shujie He; Tae Ho Lee; Lee Lee Chu; Brad Bolon; Paul Goodyer; Michael Eccles; Jerry Pelletier |
Related Documents
:
|
6179045 - 51cr-bleomycin, a new oncophilic radiopharmaceutical. i. activity concentrations in tra... 6355475 - Notes on the toxicity and carcinogenicity of some south african cycad species with spec... 2545605 - Transplantation and chromosomal analysis of cell lines derived from mesotheliomas induc... 15854185 - Laparoscopic nephrectomy: the new gold standard? 20555305 - Impact of prophylactic versus preemptive valganciclovir on long-term renal allograft ou... 17098005 - Diagnostic usefulness of inflammatory markers in acute cellular rejection after heart t... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Oncogene Volume: 22 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2003 Nov |
Date Detail:
|
Created Date: 2003-11-06 Completed Date: 2003-12-11 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
|
Languages: eng Pagination: 8145-55 Citation Subset: IM |
Affiliation:
|
Department of Biochemistry, McGill University, Montreal, Quebec, Canada. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals DNA-Binding Proteins / genetics*, metabolism Kidney / embryology Mice Mice, Inbred C57BL Mutation* PAX2 Transcription Factor Transcription Factors / genetics*, metabolism WT1 Proteins / metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/DNA-Binding Proteins; 0/PAX2 Transcription Factor; 0/Pax2 protein, mouse; 0/Transcription Factors; 0/WT1 Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Transfection of a dominant-negative mutant NF-kB inhibitor (IkBm) represses p53-dependent apoptosis ...
Next Document: Conserved SNH domain of the proto-oncoprotein SYT interacts with components of the human chromatin r...