Functions of lumican and fibromodulin: lessons from knockout mice

Glycoconj J. May-Jun 2002;19(4-5):287-93. doi: 10.1023/A:1025348417078.

Abstract

Lumican and fibromodulin are collagen-binding leucine-rich proteoglycans widely distributed in interstitial connective tissues. The phenotypes of lumican-null (Lum(-/-)), Fibromodulin-null (Fmod(-/-)) and compound double-null (Lum(-/-)Fmod(-/-)) mice identify a broad range of tissues where these two proteoglycans have overlapping and unique roles in modulating the extracellular matrix and cellular behavior. The lumican-deficient mice have reduced corneal transparency and skin fragility. The Lum(-/-)Fmod(-/-) mice are smaller than their wildtype littermates, display gait abnormality, joint laxity and age-dependent osteoarthritis. Misaligned knee patella, severe knee dysmorphogenesis and extreme tendon weakness are the likely cause for joint-laxity. Fibromodulin deficiency alone leads to significant reduction in tendon stiffness in the Lum(+/+)Fmod(-/-) mice, with further loss in stiffness in a lumican gene dose-dependent way. At the level of ultrastructure, the Lum(-/-) cornea, skin and tendon show irregular collagen fibril contours and increased fibril diameter. The Fmod(-/-) tendon contains irregular contoured collagen fibrils, with increased frequency of small diameter fibrils. The tendons of Lum(-/-)Fmod(-/-) have an abnormally high frequency of small and large diameter fibrils indicating a de-regulation of collagen fibril formation and maturation. In tissues like the tendon, where both proteoglycans are present, fibromodulin may be required early in collagen fibrillogenesis to stabilize small-diameter fibril-intermediates and lumican may be needed at a later stage, primarily to limit lateral growth of fibrils

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / physiology*
  • Chondroitin Sulfate Proteoglycans / deficiency*
  • Chondroitin Sulfate Proteoglycans / genetics*
  • Chondroitin Sulfate Proteoglycans / physiology
  • Collagen / metabolism
  • Connective Tissue Diseases / genetics
  • Connective Tissue Diseases / physiopathology
  • Cornea / metabolism
  • Extracellular Matrix Proteins*
  • Fibromodulin
  • Gene Expression
  • Keratan Sulfate / deficiency*
  • Keratan Sulfate / genetics*
  • Keratan Sulfate / metabolism
  • Keratan Sulfate / physiology
  • Lumican
  • Mice
  • Mice, Knockout
  • Phenotype
  • Proteoglycans*
  • Skin / metabolism
  • Tendons / metabolism
  • Tissue Distribution

Substances

  • Carrier Proteins
  • Chondroitin Sulfate Proteoglycans
  • Extracellular Matrix Proteins
  • Fmod protein, mouse
  • Lum protein, mouse
  • Lumican
  • Proteoglycans
  • Fibromodulin
  • Collagen
  • Keratan Sulfate