Wilms’ Tumor Nephroblastoma Affects 1:10,000 children ~8% of all pediatric Malignancies 80% of these tumors can be successfully treated

WT1 Tumor Suppressor Chromosome 11 (11p13) Mutated in 5-10% of all Wilms Tumors ~50Kb 10 exons kDa 24 Isoforms

WT1 Scholz et al.

WT1 Wagner et al.

Frasier Syndrome Heterozygous loss of +KTS causes Male to Female sex reversal Wilms’ Tumor Glomerulosclerosis

WAGR Syndrome Heterozygous loss of WT1 Wilms’ Tumor Mental retardation Milder overall phenotype in kidneys and gonads than DDS and FS

Denys-Drash Syndrome Truncated Zinc-Fingers Causes normal female gonads In males, streak gonads and mild hermaphroditism Wilm’s Tumor Dominant-negative phenotype

Denys-Drash Syndrome Wild type WT1 homodimerizes Truncated WT1 dimerizes with wild type WT1, which further lowers WT1 function Truncated WT1 works in a Dominant-Negative motif

Knockout Mice Embryonic Lethal between 12 days and birth Mice had no Kidneys nor Gonads and defects in mesothelial tissue, heart, adrenal glands and spleen WT1(+KTS) lacking Mice showed disturbed podocyte function and male-to-female sex reversal WT1 (-KTS) lacking Mice showed severe kidney and gonad defects

WT1 Wagner et al.

In Conclusion WT1 is a Tumor Suppressor WT1 has 24 Isoforms WT1 interacts with DNA, RNA and other Proteins WT1 is a Transcription Factor It is an Enhancer It is a Developmental Gene

References Scharnhorst, V., Van der Eb, A., Jochemsen, A WT1 proteins: funtion in growth and differentiation. Gene: 273, p Scholz, H., Kirschner, K A Role for the Wilm’s Tumor Protein WT1 in Organ Development. Physiology 20: p Wagner, K-D., Wagner, N., Schedl, A The complex life of WT1. Journal of Cell Science: p