Functions of lumican and fibromodulin: lessons from knockout mice |
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Authors: | Chakravarti Shukti |
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Affiliation: | (1) Departments of Medicine, Cell Biology and Ophthalmology, Johns Hopkins University, Baltimore, MD, USA |
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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 Published in 2003. |
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Keywords: | lumican fibromodulin gene targeted mouse connective tissue defect collagen fibril abnormalities SLRP (small leucine-rich repeat proteoglycans) |
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