MUSCLE-SPECIFIC EXPRESSION OF A DOMINANT-NEGATIVE DESMIN MUTANT IN TRANSGENIC MICE

To extend our knowledge of the functions of desmin and vimentin interm ediate filaments in the developing organism, a construct encoding a tr uncated desmin subunit driven by the desmin promoter (pDDV), was intro duced into the murine germ line. The resulting mutant desmin subunit w as assembly-incompetent and capable of disrupting both preexisting des min and vimentin filaments in a dominant negative fashion in transfect ed C2C12 muscle cells and in transgenic mouse muscle tissue. Expressio n of the pDDV was tissue-specific in transgenic mice. High level expre ssion of pDDV occurred in a small percentage of desmin-containing musc le cells. Immunohistochemical staining of muscle tissue showed a diffu se desmin pattern instead of the dots and clumps into which mutant des min typically accumulates in undifferentiated C2C12 muscle cells in ti ssue culture. Disruption of the endogenous desmin filaments in Sartori us muscle results in ultrastructural abnormalities.