Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation.
basic_science · Level V
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Abstract
Alternative splicing of Wt1 results in the insertion or omission of the three amino acids KTS between zinc fingers 3 and 4. In vitro experiments suggest distinct molecular functions for + and -KTS isoforms. We have generated mouse strains in which specific isoforms have been removed. Heterozygous mice with a reduction of +KTS levels develop glomerulosclerosis and represent a model for Frasier syndrome. Homozygous mutants of both strains die after birth due to kidney defects. Strikingly, mice lacking +KTS isoforms show a complete XY sex reversal due to a dramatic reduction of Sry expression levels. Our data demonstrate distinct functions for the two splice variants and place the +KTS variants as important regulators for Sry in the sex determination pathway.
Medical subject headings
- Alternative Splicing
- DNA-Binding Proteins
- Genes, Wilms Tumor
- Nephrons
- Nuclear Proteins
- Repressor Proteins
- Sex Determination Processes
- Transcription Factors