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Cell. 2001 Aug 10;106(3):319-29.

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

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1
MDC for Molecular Medicine, Developmental Genetics, Robert-Rössle-Str. 10, 13092 Berlin, Germany.

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.

PMID:
11509181
[Indexed for MEDLINE]
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