MECHANICAL ALTERATIONS IN SMOOTH-MUSCLE FROM MICE LACKING DESMIN

Mice with a null mutation introduced in the desmin gene were used to s tudy the mechanical role of intermediate filaments in smooth muscle ce lls. Vas deferens (VD), urinary bladder (UB) and portal vein (PV) prep arations were obtained from adult animals lacking desmin (Des -/-) and from age-and weight-matched wild-type animals (Des +/+). Active force per cross-sectional area was decreased in the smooth muscle of the De s -/- compared with Des +/+ mice CVD to 42%; UB to 34%). Quantitative gel electrophoresis suggests a marginally lower cellular content of my osin, but the organization of the contractile apparatus appeared uncha nged by electron microscopy. A similar reduction in stress was measure d in Des -/- skinned fibres showing that altered activation mechanisms were not involved. The results indicate that the reduced active force is caused by low intrinsic force generation of the contractile filame nts or subtle modifications in the coupling between the contractile el ements and the cytoskeleton. The relationship between length and passi ve stress was less steep in the Des -/- samples and a second length fo rce curve after maximal extension revealed a loss of passive stress. T he maximal shortening velocity was reduced in Des -/- skinned VD and U B preparations by approximately 25-40%. This was associated with an in creased relative content of the basic essential myosin Light chain, su ggesting that alterations in the contractile system towards a slower, more economical muscle had occurred. PV preparations showed no differe nce in mechanical properties in Des +/+ and Des -/- animals, a result that was consistent with the predominance of vimentin instead of desmi n in this vascular tissue. In conclusion, the results show that, altho ugh intermediate filaments in smooth muscle are not required for force generation or maintenance of passive tension, they have a role in cel lular transmission of both active and passive force. (C) Chapman & Hal l Ltd.