Loss of SM-B myosin affects muscle shortening velocity and maximal force development

Nat Cell Biol. 2001 Nov;3(11):1025-9. doi: 10.1038/ncb1101-1025.

Abstract

We used an exon-specific gene-targeting strategy to generate a mouse model deficient only in the SM-B myosin isoform. Here we show that deletion of exon-5B (specific for SM-B) in the gene for the heavy chain of smooth muscle myosin results in a complete loss of SM-B myosin and switching of splicing to the SM-A isoform, without affecting SM1 and SM2 myosin content. Loss of SM-B myosin does not affect survival or cause any overt smooth muscle pathology. Physiological analysis reveals that absence of SM-B myosin results in a significant decrease in maximal force generation and velocity of shortening in smooth muscle tissues. This is the first in vivo study to demonstrate a functional role for the SM-B myosin isoform. We conclude that the extra seven-residue insert in the surface loop 1 of SM-B myosin is a critical determinant of crossbridge cycling and velocity of shortening.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Gene Expression
  • Heart / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiology*
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • RNA Splicing
  • Smooth Muscle Myosins / genetics
  • Smooth Muscle Myosins / physiology*
  • Urinary Bladder / metabolism

Substances

  • Protein Isoforms
  • Smooth Muscle Myosins