Fig. 1. Model for splice-specific functions of WT1. The mammalian WT1 gene consists of 10 exons. Post-transcriptional modifications result in the generation of 24 isoforms. Exons 5 and 9 are alternatively spliced. Exon 5 encodes 17 additional amino acids; the use of alternative splice donor site 2 of exon 9 results in inclusion of the three amino acids lysine, threonine and serine (+KTS). The ratio between WT1(+KTS) and WT1(-KTS) proteins is nearly constant in all cell types, whereas the ratio of exon 5 splice variants differs. It is speculated that alternative splicing of exon 5 has a modulatory role on WT1 function; the -KTS variant acts as transcriptional regulator; and the +KTS splice variant might have a role in RNA processing. In mouse strains, which specifically lack the WT1(-KTS) or WT1(+KTS) splice variant, the urogenital phenotype is more severe in mice lacking the WT1(-KTS) variant. Animals lacking the WT1(+KTS) variant represent a mouse model for the human Frasier syndrome.