Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican.
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.
Chakravarti
S
S
Department of Medicine and Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4952, USA. sxc76@po.cwru.edu
Magnuson
T
T
Lass
J H
JH
Jepsen
K J
KJ
LaMantia
C
C
Carroll
H
H
D000818:Animals; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000502:physiology*; D003094:Collagen / Q000378:metabolism*; D003318:Corneal Opacity / Q000209:etiology* / Q000473:pathology; D015870:Gene Expression; D018390:Gene Targeting; D017403:In Situ Hybridization; D007632:Keratan Sulfate / Q000235:genetics / Q000502:physiology*; D000071234:Lumican; D051379:Mice; D012875:Skin Diseases, Metabolic / Q000209:etiology* / Q000473:pathology; D013718:Tensile Strength
D011508:Chondroitin Sulfate Proteoglycans; C000604307:Lum protein, mouse; D000071234:Lumican; D003094:Collagen; D007632:Keratan Sulfate