Homozygous cpk/cpk mice develop
polycystic kidney disease and die of
uremia between the fourth and fifth weeks of age. Cpk/cpk mice treated weekly with
paclitaxel (
Taxol) can live to over six months of age. This dramatic moderation of
polycystic kidney disease progression has been postulated to be a result of
paclitaxel's ability to stabilize microtubules. In this study, the ability of
taxanes with differing abilities to promote spontaneous in vitro assembly of
tubulin dimers into microtubules were tested for their ability to inhibit the progression of
polycystic kidney disease in polycystic cpk/cpk mice. We found that
taxanes that are active in promoting microtubule assembly, including
paclitaxel, 10-deactyl-taxol and
cephalomannine increased the survival of polycystic cpk/cpk mice significantly longer than control animals. In contrast, the microtubule inactive
taxane baccatin-III has no effect on the progression of
renal failure in cpk/cpk mice. We conclude that the ability to promote microtubule assembly may be necessary for
paclitaxel and related
taxanes to modulate the progression of
polycystic kidney progression in cpk/cpk mice.