Mouse development is not obviously affected by the absence of dermatan sulfate epimerase 2 in spite of a modified brain dermatan sulfate composition
Mouse development is not obviously affected by the absence of dermatan sulfate epimerase 2 in spite of a modified brain dermatan sulfate composition
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DOI：
10.1093/glycob/cws065
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发表时间：
2012-07-01
期刊：
影响因子：
4.3
通讯作者：
Maccarana, Marco
中科院分区：
文献类型：
--
作者：
Bartolini, Barbara;Thelin, Martin A.;Maccarana, Marco
硫酸皮肤素差向异构酶2(DS-EPEP2)与其同系物DS-EPEP1一起，在DS多糖链中将葡萄糖醛酸转化为艾杜糖酸。硬脂酸增加了DS链的灵活性，促进了蛋白质的结合。DS-ep2在脑中广泛表达，是脑内最主要的差向异构酶。在这里，我们报告了DS-EP2缺失小鼠的产生和初步特征。DS-ep2基因缺陷小鼠在解剖学、组织学或形态上均未见异常。突变型和野生型窝仔的体重和身长难以区分。他们很能生育，并且有正常的寿命。从新生突变小鼠脑中分离到的硫酸软骨素(CS/DS)与野生型相比，艾杜糖酸减少了38%，成分分析表明4-O-硫酸盐减少，6-O-硫酸盐结构增加。尽管艾杜糖醛酸减少，但免疫组织学染色显示，成年DS-ep2-/-脑显示正常的细胞外基质特征。我们认为DS-EP1在体内对DS-EP2的丢失具有代偿作用。这些结果扩展了先前关于脑细胞外基质成分功能冗余的发现。
Dermatan sulfate epimerase 2 (DS-epi2), together with its homolog DS-epi1, transform glucuronic acid into iduronic acid in DS polysaccharide chains. Iduronic acid gives DS increased chain flexibility and promotes protein binding. DS-epi2 is ubiquitously expressed and is the predominant epimerase in the brain. Here, we report the generation and initial characterization of DS-epi2 null mice. DS-epi2-deficient mice showed no anatomical, histological or morphological abnormalities. The body weights and lengths of mutated and wild-type littermates were indistinguishable. They were fertile and had a normal lifespan. Chondroitin sulfate (CS)/DS isolated from the newborn mutated mouse brains had a 38% reduction in iduronic acid compared with wild-type littermates, and compositional analysis revealed a decrease in 4-O-sulfate and an increase in 6-O-sulfate containing structures. Despite the reduction in iduronic acid, the adult DS-epi2-/- brain showed normal extracellular matrix features by immunohistological stainings. We conclude that DS-epi1 compensates in vivo for the loss of DS-epi2. These results extend previous findings of the functional redundancy of brain extracellular matrix components.