Gilmour D T, Lyon G J, Carlton M B, Sanes J R, Cunningham J M, Anderson J R, Hogan B L, Evans M J, Colledge W H
Wellcome/CRC Institute of Cancer and Developmental Biology and Department of Genetics, University of Cambridge, Tennis Court Rd, Cambridge CB2 3QR.
EMBO J. 1998 Apr 1;17(7):1860-70. doi: 10.1093/emboj/17.7.1860.
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 (Sparctm1Cam) 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.
SPARC（分泌性酸性富含半胱氨酸蛋白，也称为骨连接蛋白/BM40）是一种分泌型钙结合糖蛋白，可与一系列细胞外基质分子相互作用，包括IV型胶原蛋白。它在胚胎发育过程中广泛表达，体外研究表明其在调节细胞黏附与增殖以及调节细胞因子活性方面发挥作用。为了分析该蛋白在体内的功能，通过小鼠胚胎干细胞中的同源重组破坏了内源性Sparc基因座。SPARC缺陷小鼠（Sparctm1Cam）在6个月龄左右之前看起来正常且可育，之后会出现严重的眼部病变，其特征为白内障形成和晶状体囊破裂。晶状体病变的首个迹象出现在赤道弓区域，在分化的上皮细胞和纤维细胞内逐渐形成空泡。然而，晶状体囊在主要基底膜蛋白层粘连蛋白、IV型胶原蛋白、基底膜聚糖或巢蛋白中未显示出质性变化。这些小鼠是进一步研究SPARC如何在体内影响细胞行为的极佳资源。
