International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

G14 Characterisation of Transgenic Mice Overexpressing the Wilms' Tumour Protein WT1

James Dutton and Andrew Ward. University of Bath, UK

Expression of the product of the Wilms' tumour gene WT1 is essential for correct mammalian genito-urinary development. Homozygous WT1 null mice do not develop kidneys or gonads and die during embroyogenesis. The WT1 gene encodes multiple isoforms of a Kruppel-type transcription factor containing four C2H2 zinc-fingers. The various WT1 isoforms are thought to perform different gene regulatory roles by nucleic acid binding and association with splicing factors.

We have identified amino acids in zinc finger 1 that are essential for binding both DNA and RNA and illustrate their importance in WT1 function. The tissue-specific ratios of WT1 isoform expression are tightly regulated during development. In humans, perturbation of these ratios causes Frasier Syndrome characterised by developmental defects of the kidney and urogenital tract. We have derived lines of transgenic mice that overexpress a single WT1 isoform under the control of an embryonic Igf2 promoter.

Here we describe the phenotypes of these mice and illustrate the effect of ectopic WT1 expression during embryonic development in both wild-type mice and in the absence of endogenous WT1 expression.

 


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