title: Skeletal muscle weakness in osteogenesis imperfecta mice.
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.
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65211, USA. weberb@missouri.edu
authors.forename: Bettina A
authors.initials: BA
authors.lastname: Gentry
authors.forename: J Andries
authors.initials: JA
authors.lastname: Ferreira
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: McCambridge
authors.forename: Marybeth
authors.initials: M
authors.lastname: Brown
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D003094:Collagen / Q000235:genetics*; D024042:Collagen Type I; D005260:Female; D024022:Fibrillar Collagens / Q000032:analysis; D016368:Frameshift Mutation / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009119:Muscle Contraction / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D018908:Muscle Weakness / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009218:Myosins / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
chemical_list: D024042:Collagen Type I; D024022:Fibrillar Collagens; D003094:Collagen; D009218:Myosins