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Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation.

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.

Pubmed ID: 11509181


  • Hammes A
  • Guo JK
  • Lutsch G
  • Leheste JR
  • Landrock D
  • Ziegler U
  • Gubler MC
  • Schedl A



Publication Data

August 10, 2001

Associated Grants


Mesh Terms

  • Active Transport, Cell Nucleus
  • Alternative Splicing
  • Animals
  • Animals, Newborn
  • Apoptosis
  • Base Sequence
  • Cell Survival
  • DAX-1 Orphan Nuclear Receptor
  • DNA-Binding Proteins
  • Disorders of Sex Development
  • Exons
  • Female
  • Genes, Wilms Tumor
  • Glomerulosclerosis, Focal Segmental
  • Gonads
  • Male
  • Mice
  • Mutagenesis
  • Nephrons
  • Nuclear Proteins
  • Protein Isoforms
  • RNA Splice Sites
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Sex Determination Processes
  • Sex-Determining Region Y Protein
  • Syndrome
  • Transcription Factors
  • WT1 Proteins