|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
doi: 10.1242/10.1242/jcs.00405
Commentary |
1 Johannes-Müller-Institut für Physiologie, Medizinische Fakultät
(Charité), Humboldt-Universität Berlin, Germany
2 University of Nice, INSERM U470, 06108 Nice, France
* Author for correspondence (e-mail: schedl{at}unice.fr)
The Wilms' tumour gene, WT1, encodes a zinc-finger transcription factor that is inactivated in a subset of Wilms' tumours. Mutation analysis in human patients and genetic experiments in mice have revealed that WT1 has a role much wider than just tumour suppression. Alternative splicing, RNA editing, and the use of alternative translation initiation sites generate a multitude of isoforms, which seem to have overlapping but also distinct functions during embryonic development and the maintenance of organ function. Recently, mouse strains lacking the WT1(-KTS) or WT1(+KTS) splice variants of exon 9 were generated. More severe defects of kidneys and gonads are found in mice lacking the WT1(-KTS) variant. Animals lacking the WT1(+KTS) variant show disturbed podocyte function and male-to-female sex reversal. Alternative splicing of exon 5, however, might not modify WT1 function dramatically. Recently, it was also described that reduction of WT1 levels in the kidney results in glomerulosclerosis and upregulation of WT1 in the heart might contribute to neovascularization after infarction.
Key words: Splice-specific functions, Glomerulosclerosis, Knockout mouse models, Frasier syndrome, Denys-Drash syndrome, Sex determination
This article has been cited by other articles:
|
|
 |
|
  T. Tanaka, S. Gondo, T. Okabe, K. Ohe, H. Shirohzu, H. Morinaga, M. Nomura, K. Tani, R. Takayanagi, H. Nawata, et al. Steroidogenic factor 1/adrenal 4 binding protein transforms human bone marrow mesenchymal cells into steroidogenic cells J. Mol. Endocrinol., November 1, 2007; 39(5): 343 - 350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-S. Kim, M. S. Kim, A. L. Hancock, J. C. P. Harper, J. Y. Park, G. Poy, A. O. Perantoni, M. Cam, K. Malik, and S. B. Lee Identification of Novel Wilms' Tumor Suppressor Gene Target Genes Implicated in Kidney Development J. Biol. Chem., June 1, 2007; 282(22): 16278 - 16287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kohler, A.-L. Delezoide, B. Boizet-Bonhoure, M. J McPhaul, C. Sultan, and S. Lumbroso Coexpression of Wilms' tumor suppressor 1 (WT1) and androgen receptor (AR) in the genital tract of human male embryos and regulation of AR promoter activity by WT1 J. Mol. Endocrinol., May 1, 2007; 38(5): 547 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Hancock, K. W. Brown, K. Moorwood, H. Moon, C. Holmgren, S. H. Mardikar, A. R. Dallosso, E. Klenova, D. Loukinov, R. Ohlsson, et al. A CTCF-binding silencer regulates the imprinted genes AWT1 and WT1-AS and exhibits sequential epigenetic defects during Wilms' tumourigenesis Hum. Mol. Genet., February 1, 2007; 16(3): 343 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Matsushita, T. Tomonaga, H. Shimada, A. Shioya, M. Higashi, H. Matsubara, K. Harigaya, F. Nomura, D. Libutti, D. Levens, et al. An Essential Role of Alternative Splicing of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor in Carcinogenesis Cancer Res., February 1, 2006; 66(3): 1409 - 1417. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Orloff, S. K. Iyengar, C. A. Winkler, K. A. B. Goddard, R. A. Dart, T. S. Ahuja, M. Mokrzycki, W. A. Briggs, S. M. Korbet, P. L. Kimmel, et al. Variants in the Wilms' tumor gene are associated with focal segmental glomerulosclerosis in the African American population Physiol Genomics, April 14, 2005; 21(2): 212 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Hammer, K. L. Parker, and B. P. Schimmer Minireview: Transcriptional Regulation of Adrenocortical Development Endocrinology, March 1, 2005; 146(3): 1018 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. P. Michael, L. Kurlender, N. Memari, G. M. Yousef, D. Du, L. Grass, C. Stephan, K. Jung, and E. P. Diamandis Intron Retention: A Common Splicing Event within the Human Kallikrein Gene Family Clin. Chem., March 1, 2005; 51(3): 506 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Rubera, C. Poujeol, G. Bertin, L. Hasseine, L. Counillon, P. Poujeol, and M. Tauc Specific Cre/Lox Recombination in the Mouse Proximal Tubule J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2050 - 2056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Borgono, I. P. Michael, and E. P. Diamandis Human Tissue Kallikreins: Physiologic Roles and Applications in Cancer Mol. Cancer Res., May 1, 2004; 2(5): 257 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Srichai, M. Konieczkowski, A. Padiyar, D. J. Konieczkowski, A. Mukherjee, P. S. Hayden, S. Kamat, M. A. El-Meanawy, S. Khan, P. Mundel, et al. A WT1 Co-regulator Controls Podocyte Phenotype by Shuttling between Adhesion Structures and Nucleus J. Biol. Chem., April 2, 2004; 279(14): 14398 - 14408. [Abstract] [Full Text] [PDF]
|
|
