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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
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