DISRUPTION OF VIMENTIN INTERMEDIATE FILAMENTS IN TRANSGENIC MICE BY EXPRESSION OF A DOMINANT-NEGATIVE MUTANT DESMIN SUBUNIT

To investigate putative functions of vimentin intermediate filaments i n the context of intact tissues and the developing organism, a constru ct (pVDV), driven by the vimentin promoter and encoding a truncated de smin subunit, was introduced into the murine germ line. The mutant des min was assembly-incompetent and capable of disrupting preexisting vim entin filaments in a dominant negative fashion, both in transgenic mou se tissues and in fibroblast cultures derived from these mice. Mutant desmin expression strongly enhanced vimentin turnover. In tissues of s ome transgenic mouse lines, high level expression of pVDV occurred in 10 to 40 % of vimentin-containing cells and, surprisingly in 1 to 10 % of the skeletal and tongue muscle cells. Immunohistochemical staining of muscle tissue showed a diffuse staining pattern instead of the pun ctated aggregates into which mutant desmin typically accumulates in ot her cell types. The overexpression of pVDV and the concomitant disrupt ion of the endogenous vimentin filament network and enhanced vimentin turnover in a significant percentage of cells did not cause detectable developmental abnormalities.