Altered collagen fibril formation in the sclera of lumican-deficient mice.
Altered collagen fibril formation in the sclera of lumican-deficient mice.
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发表时间：
2002-06
影响因子：
4.4
通讯作者：
B. A. Austin;C. Coulon;Chia-Yang Liu;W. Kao;J. Rada
中科院分区：
文献类型：
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作者：
B. A. Austin;C. Coulon;Chia-Yang Liu;W. Kao;J. Rada
为了更好地了解lumican（角膜硫酸角蛋白聚糖）在巩膜细胞外基质中的作用，我们在野生型小鼠和lumican基因纯合或杂合的小鼠的巩膜中评估了胶原纤维的大小、形状和组织。方法。采用透射电镜对6月龄野生型（lum+/lum+）和lumica缺失型（lum+/lum-和lum-/lum-）小鼠前后巩膜进行分析。此外，通过Western blot分析，在野生型和鲁米肯蛋白缺乏小鼠的巩膜中发现了鲁米肯蛋白。结果：Lumican以大约48kda的核心蛋白形式存在于小鼠巩膜中，该核心蛋白含有短的糖胺聚糖侧链，由中至低硫酸角蛋白硫酸盐组成。野生型小鼠巩膜由不规则排列的胶原原纤维片组成，前巩膜平均直径为47.37 +/- 0.648 nm，后巩膜平均直径为54.68 +/- 0.342 nm。lumican突变小鼠（lum+/lum-和lum-/lum-）巩膜前区和后区胶原纤维直径均显著大于野生型小鼠（分别为72.61 +/- 0.445和84.47 +/- 0.394 nm），差异有统计学意义（P < 0.001）。结论：本研究结果表明，lumican基因一个或两个等位基因的零突变导致巩膜胶原纤维形成的显著缺陷，可能导致眼形状和大小的改变，严重影响视力。
PURPOSE To better understand the role of lumican (corneal keratan sulfate proteoglycan) in the scleral extracellular matrix, collagen fibril size, shape, and organization were evaluated in the sclera of wild-type mice and in mice homozygous or heterozygous for a null mutation in the lumican gene. METHODS. Anterior and posterior sclera from 6-month-old wild-type (lum+/lum+) and lumican-deficient mice (lum+/lum- and lum-/lum-) were analyzed by transmission electron microscopy. In addition, lumican was characterized in the sclera of wild-type and lumican-deficient mice by Western blot analyses. RESULTS Lumican was present in the mouse sclera as an approximately 48-kDa core protein containing short glycosaminoglycan side chains consisting of moderate- to low-sulfated keratan sulfate. The wild-type mouse sclera consisted of irregularly arranged lamellae of collagen fibrils with an average diameter of 47.37 +/- 0.648 nm in the anterior sclera and 54.68 +/- 0.342 nm the posterior sclera. Collagen fibrils in the sclera of lumican mutant mice (lum+/lum- and lum-/lum-) were significantly larger in diameter in anterior (72.61 +/- 0.445 and 84.47 +/- 0.394 nm, respectively) and posterior (75.92 +/- 0.361 and 80.90 +/- 0.490 nm, respectively) scleral regions compared with wild-type mice (P < 0.001). CONCLUSIONS The results of the present study indicate that null mutations in one or both alleles of the lumican gene result in significant defects in scleral collagen fibril formation that could lead to alterations in ocular shape and size and severely affect vision.