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      Targeted deletion of collagen V in tendons and ligaments results in a classic Ehlers-Danlos syndrome joint phenotype.

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          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.

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          Author and article information

          Journal
          Am. J. Pathol.
          The American journal of pathology
          1525-2191
          0002-9440
          May 2015
          : 185
          : 5
          Affiliations
          [1 ] Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida.
          [2 ] McKay Orthopedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania.
          [3 ] Myriad Genetic Laboratories, Salt Lake City, Utah.
          [4 ] Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, Tampa, Florida. Electronic address: dbirk@health.usf.edu.
          Article
          S0002-9440(15)00130-3
          10.1016/j.ajpath.2015.01.031
          25797646
          Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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