Mice deficient for the secreted glycoprotein SPARC/osteonectin/BM40 develop normally but show severe age-onset cataract formation and disruption of the lens
Mice deficient for the secreted glycoprotein SPARC/osteonectin/BM40 develop normally but show severe age-onset cataract formation and disruption of the lens
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DOI：
10.1093/emboj/17.7.1860
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发表时间：
1998-04-01
期刊：
影响因子：
11.4
通讯作者：
Colledge, WH
中科院分区：
文献类型：
--
作者：
Gilmour, DT;Lyon, GJ;Colledge, WH
SPARC（富含半胱氨酸的酸性分泌蛋白，也称为骨连接蛋白/BM40）是一种分泌型 Ca2+ 结合糖蛋白，可与一系列细胞外基质分子（包括 IV 型胶原）相互作用。它在胚胎发生过程中广泛表达，体外研究表明其在细胞粘附和增殖的调节以及细胞因子活性的调节中发挥作用。为了分析该蛋白在体内的功能，通过在小鼠胚胎干细胞中进行同源重组来破坏内源性 Sparc 基因座。 SPARC 缺陷小鼠 (Sparc(tm1Cam)) 在 6 个月左右之前表现正常且具有生育能力，此时它们会出现以白内障形成和晶状体囊破裂为特征的严重眼部病变。晶状体病理学的第一个迹象发生在赤道弓区域，其中在分化的上皮细胞和纤维细胞内逐渐形成液泡。然而，晶状体囊的主要基底层蛋白层粘连蛋白、IV 型胶原蛋白、基底膜蛋白或巢蛋白没有显示出质的变化。这些小鼠是进一步研究 SPARC 如何影响体内细胞行为的极好资源。
SPARC (secreted protein acidic and rich in cysteine, also known as osteonectin/BM40) is a secreted Ca2+-binding glycoprotein that interacts with a range of extracellular matrix molecules, including collagen IV. It is widely expressed during embryogenesis, and in vitro studies have suggested roles in the regulation of cell adhesion and proliferation, and in the modulation of cytokine activity. In order to analyse the function of this protein in vivo, the endogenous Sparc locus was disrupted by homologous recombination in murine embryonic stem cells. SPARC-deficient mice (Sparc(tm1Cam)) appear normal and fertile until around 6 months of age, when they develop severe eye pathology characterized by cataract formation and rupture of the lens capsule. The first sign of lens pathology occurs in the equatorial bow region where vacuoles gradually form within differentiating epithelial cells and fibre cells. The lens capsule, however, shows no qualitative changes in the major basal lamina proteins laminin, collagen IV, perlecan or entactin. These mice are an excellent resource for further studies on how SPARC affects cell behaviour in vivo.