Skeletal muscle weakness in osteogenesis imperfecta mice

Matrix Biol. 2010 Sep;29(7):638-44. doi: 10.1016/j.matbio.2010.06.006. Epub 2010 Jul 6.

Abstract

Exercise intolerance, muscle fatigue and weakness are often-reported, little-investigated concerns of patients with osteogenesis imperfecta (OI). OI is a heritable connective tissue disorder hallmarked by bone fragility resulting primarily from dominant mutations in the proα1(I) or proα2(I) collagen genes and the recently discovered recessive mutations in post-translational modifying proteins of type I collagen. In this study we examined the soleus (S), plantaris (P), gastrocnemius (G), tibialis anterior (TA) and quadriceps (Q) muscles of mice expressing mild (+/oim) and moderately severe (oim/oim) OI for evidence of inherent muscle pathology. In particular, muscle weight, fiber cross-sectional area (CSA), fiber type, fiber histomorphology, fibrillar collagen content, absolute, relative and specific peak tetanic force (P(o), P(o)/mg and P(o)/CSA respectively) of individual muscles were evaluated. Oim/oim mouse muscles were generally smaller, contained less fibrillar collagen, had decreased P(o) and an inability to sustain P(o) for the 300-ms testing duration for specific muscles; +/oim mice had a similar but milder skeletal muscle phenotype. +/oim mice had mild weakness of specific muscles but were less affected than their oim/oim counterparts which demonstrated readily apparent skeletal muscle pathology. Therefore muscle weakness in oim mice reflects inherent skeletal muscle pathology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight / genetics
  • Collagen / genetics*
  • Collagen Type I
  • Female
  • Fibrillar Collagens / analysis
  • Frameshift Mutation / genetics
  • Heterozygote
  • Homozygote
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Muscle Contraction / physiology
  • Muscle Fibers, Skeletal / pathology
  • Muscle Weakness / genetics*
  • Muscle Weakness / pathology
  • Muscle Weakness / physiopathology
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Myosins / metabolism
  • Osteogenesis Imperfecta / genetics
  • Osteogenesis Imperfecta / pathology
  • Osteogenesis Imperfecta / physiopathology*

Substances

  • Collagen Type I
  • Fibrillar Collagens
  • Collagen
  • Myosins