title: Targeted deletion of collagen V in tendons and ligaments results in a classic Ehlers-Danlos syndrome joint phenotype.
abstract: Collagen V mutations underlie classic Ehlers-Danlos syndrome, and joint hypermobility is an important clinical manifestation. We define the function of collagen V in tendons and ligaments, as well as the role of alterations in collagen V expression in the pathobiology in classic Ehlers-Danlos syndrome. A conditional Col5a1(flox/flox) mouse model was bred with Scleraxis-Cre mice to create a targeted tendon and ligament Col5a1-null mouse model, Col5a1(Δten/Δten). Targeting was specific, resulting in collagen V-null tendons and ligaments. Col5a1(Δten/Δten) mice demonstrated decreased body size, grip weakness, abnormal gait, joint laxity, and early-onset osteoarthritis. These gross changes were associated with abnormal fiber organization, as well as altered collagen fibril structure with increased fibril diameters and decreased fibril number that was more severe in a major joint stabilizing ligament, the anterior cruciate ligament (ACL), than in the flexor digitorum longus tendon. The ACL also had a higher collagen V content than did the flexor digitorum longus tendon. The collagen V-null ACL and flexor digitorum longus tendon both had significant alterations in mechanical properties, with ACL exhibiting more severe changes. The data demonstrate critical differential regulatory roles for collagen V in tendon and ligament structure and function and suggest that collagen V regulatory dysfunction is associated with an abnormal joint phenotype, similar to the hypermobility phenotype in classic Ehlers-Danlos syndrome.
authors: Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors: Mei
authors: M
authors: Sun
authors: McKay Orthopedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Brianne K
authors: BK
authors: Connizzo
authors: Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors: Sheila M
authors: SM
authors: Adams
authors: McKay Orthopedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Benjamin R
authors: BR
authors: Freedman
authors: Myriad Genetic Laboratories, Salt Lake City, Utah.
authors: Richard J
authors: RJ
authors: Wenstrup
authors: McKay Orthopedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Louis J
authors: LJ
authors: Soslowsky
authors: Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida. Electronic address: dbirk@health.usf.edu.
authors: David E
authors: DE
authors: Birk
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D024062:Collagen Type V / Q000172:deficiency*; D004195:Disease Models, Animal; D004535:Ehlers-Danlos Syndrome / Q000473:pathology* / Q000503:physiopathology*; D005684:Gait / Q000502:physiology; D018737:Hand Strength / Q000502:physiology; D015151:Immunoblotting; D007150:Immunohistochemistry; D007596:Joints; D008022:Ligaments / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D013710:Tendons / Q000473:pathology
chemical_list: D024062:Collagen Type V