Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation.
Journal:
Cell 2001 AugAuthors:
Hammes A, Guo JK, Lutsch G, Leheste JR, Landrock D, Ziegler U, Gubler MC, Schedl A
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 lac
...[more]king +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.[less]
Mesh Headings:
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