Keratocan-deficient mice display alterations in corneal structure

被引:155
作者
Liu, CY
Birk, DE
Hassell, JR
Kane, B
Kao, WWY
机构
[1] Univ Miami, Sch Med,Dept Ophthalmol, Bascom Palmer Eye Inst, McKnight Vis Res Ctr, Miami, FL 33136 USA
[2] Univ Miami, Sch Med, Bascom Palmer Eye Inst, Dept Cell Biol & Anat, Miami, FL 33136 USA
[3] Univ Miami, Sch Med, Bascom Palmer Eye Inst, Dept Mol & Cellular Pharmacol, Miami, FL 33136 USA
[4] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA
[5] Univ S Florida, Shriners Hosp Children Tampa, Coll Med, Tampa, FL 33612 USA
[6] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH 45267 USA
关键词
D O I
10.1074/jbc.M301169200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Keratocan ( Kera) is a cornea- specific keratan sulfate proteoglycan ( KSPG) in the adult vertebrate eye. It belongs to the small leucine- rich proteoglycan ( SLRP) gene family and is one of the major components of extracellular KSPG in the vertebrate corneal stroma. The Kera gene is expressed in ocular surface tissues including cornea and eyelids during morphogenesis. Corneal KSPGs play a pivotal role in matrix assembly, which is accountable for corneal transparency. In humans, mutations of the KERA gene are associated with cornea plana ( CNA2) that manifests decreases in vision acuity due to the flattened forward convex curvature of cornea. To investigate the biological role of the Kera gene and to establish an animal model for corneal plana, we generated Kera knockout mice via gene targeting. Northern and Western blotting and immunohistochemical analysis showed that no Kera mRNA or keratocan protein was detected in the Kera (-/-) cornea. The expression levels of other SLRP members including lumican, decorin, and fibromodulin were not altered in the Kera (-/-) cornea as compared with that of the wild- type littermates. Mice lacking keratocan have normal corneal transparency at the age of 12 months. However, they have a thinner corneal stroma and a narrower cornea-iris angle of the anterior segment in comparison to the wild- type littermates. As demonstrated by transmission electron microscopy, Kera (-/-) mice have larger stromal fibril diameters and less organized packing of collagen fibrils in stroma than those of wild type. Taken together, our results showed that ablation of the Kera gene resulted in subtle structural alterations of collagenous matrix and did not perturb the expression of other SLRPs in cornea. Keratocan thus plays a unique role in maintaining the appropriate corneal shape to ensure normal vision.
引用
收藏
页码:21672 / 21677
页数:6
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