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Abstract
The WT1 tumor suppressor gene is a zinc finger-containing transcription factor which is required for development of the kidney and gonads. A mammal-specific alternative splicing event within this gene results in the presence or absence of a 17-amino-acid sequence within the WT1 protein. To determine the function of this sequence in vivo, gene targeting was utilized to specifically eliminate the exon encoding this sequence in mice. Mice lacking WT1 exon 5 develop normally. Adult mice lacking this exon are viable and fertile, and females are capable of lactation.
We thank T. Thompson and H. Ye at the Children's Hospital Mental Retardation Research Gene Manipulation Facility for blastocyst injection, F. Alt for the gift of the pLNTK and pMCcre plasmids, R. Bronson and the Harvard Cancer Center Rodent Histopathology core for help with histological analysis, and J. Ramos for assistance with animal maintenance.
T.A.N. was supported by an American Society for Nephrology/National Kidney Foundation/SangStat fellowship. This work was supported by NIH grant DK50118.