Vaults are ribonucleoprotein particles with a distinct structure and a
high degree of conservation between species. Although no function has been
assigned to the complex yet, there is some evidence for a role of vaults
in multidrug resistance. To confirm a direct relation between vaults and
multidrug resistance, and to investigate other possible functions of
vaults, we have generated a major vault protein (MVP/lung
resistance-related protein) knockout mouse model. The MVP(-/-) mice are
viable, healthy, and show no obvious abnormalities. We investigated the
sensitivity of MVP(-/-) embryonic stem cells and bone marrow cells derived
from the MVP-deficient mice to various cytostatic agents with different
mechanisms of action. Neither the MVP(-/-) embryonic stem cells nor the
MVP(-/-) bone marrow cells showed an increased sensitivity to any of the
drugs examined, as compared with wild-type cells. Furthermore, the
activities of the ABC-transporters P-glycoprotein, multidrug
resistance-associated protein and breast cancer resistance protein were
unaltered on MVP deletion in these cells. In addition, MVP wild-type and
deficient mice were treated with the anthracycline doxorubicin. Both
groups of mice responded similarly to the doxorubicin treatment. Our
results suggest that MVP/vaults are not directly involved in the
resistance to cytostatic agents