Lumican Regulates Collagen Fibril Assembly: Skin Fragility and Corneal Opacity in the Absence of Lumican

  • Shukti Chakravarti
    *Department of Medicine and Genetics, ‡Department of Genetics, §Department of Ophthalmology, and ‖Department of Orthopaedics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4952
  • Terry Magnuson
    *Department of Medicine and Genetics, ‡Department of Genetics, §Department of Ophthalmology, and ‖Department of Orthopaedics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4952
  • Jonathan H. Lass
    *Department of Medicine and Genetics, ‡Department of Genetics, §Department of Ophthalmology, and ‖Department of Orthopaedics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4952
  • Karl J. Jepsen
    *Department of Medicine and Genetics, ‡Department of Genetics, §Department of Ophthalmology, and ‖Department of Orthopaedics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4952
  • Christian LaMantia
    *Department of Medicine and Genetics, ‡Department of Genetics, §Department of Ophthalmology, and ‖Department of Orthopaedics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4952
  • Heidi Carroll
    *Department of Medicine and Genetics, ‡Department of Genetics, §Department of Ophthalmology, and ‖Department of Orthopaedics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4952

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<jats:p>Lumican, a prototypic leucine-rich proteoglycan with keratan sulfate side chains, is a major component of the cornea, dermal, and muscle connective tissues. Mice homozygous for a null mutation in lumican display skin laxity and fragility resembling certain types of Ehlers-Danlos syndrome. In addition, the mutant mice develop bilateral corneal opacification. The underlying connective tissue defect in the homozygous mutants is deregulated growth of collagen fibrils with a significant proportion of abnormally thick collagen fibrils in the skin and cornea as indicated by transmission electron microscopy. A highly organized and regularly spaced collagen fibril matrix typical of the normal cornea is also missing in these mutant mice. This study establishes a crucial role for lumican in the regulation of collagen assembly into fibrils in various connective tissues. Most importantly, these results provide a definitive link between a necessity for lumican in the development of a highly organized collagenous matrix and corneal transparency.</jats:p>

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