Disappearance of polycystic kidney disease in revertant c-myc transgenic mice

Abstract

Nineteen SBM transgenic mouse lines specifically expressing the c-myc protooncogene in renal epithelium Transgene expression is completely penetrant, leading to death from renal failure. In the course of continuous breeding of eight transgenic lines, all lines underwent spontaneous transgene mutations characterized by partial deletion and probable rearrangement of the transgene insert. Revertant mice and their progeny have no evidence of renal disease. This constitutes the first report of spontaneous mutations occurring within transgene inserts. The high spontaneous mutation frequency of 10(-2) to 10(-3) greatly exceeds that of naturally occurring mutations and is probably favored by the transgene's multiple tandem insertion. These spontaneous mutations demonstrate that the intact transgene is necessary and sufficient to produce the SBM phenotype. Further, these results implicate deregulation of factor(s) governing epithelial cell proliferation in the pathogenesis of PKD in SBM mice.