Collagen is one of the most important components of the extracellular matrix that is involved in the strength of tissues, cell adhesion and cell proliferation. Mutations in several collagen and post-translational modification enzyme genes cause Ehlers–Danlos syndrome (EDS) characterized by joint and skin hyperextensibility as well as fragility of various organs. Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) is a critical enzyme for biosynthesis of dermatan sulfate, a side chain of various proteoglycans including biglycan that regulates collagen fibrils through their interaction. Mutations in CHST14 were found to cause a new form of EDS, named musculocontractural type EDS (mcEDS-CHST14). Large subcutaneous hematomas are one of the most serious complications accompanied by decreased quality of life and potential lethality. In this study, Chst14 gene-deleted mice were expected to be an animal model of the vascular abnormalities of mcEDS-CHST14. However, only limited numbers of adult mice were generated because of perinatal lethality in most Chst14 gene-deleted homozygote (Chst14^−/−) mice. Therefore, we investigated the placentas of these fetuses. The placentas of Chst14^−/− fetuses showed a reduced weight, alterations in the vascular structure, and ischemic and/or necrotic-like changes. Electron microscopy demonstrated an abnormal structure of the basement membrane of capillaries in the placental villus. These findings suggest that Chst14 is essential for placental vascular development and perinatal survival of fetuses. Furthermore, placentas of Chst14^−/− fetuses could be a useful model for vascular manifestations in mcEDS-CHST14, such as the large subcutaneous hematomas.

中文翻译：

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Chst14 ^-/-胎儿胎盘中的血管异常：对人类CHST14 / D4ST1缺乏症的鼠模型围生期致死性的病理生理和血管病变的影响

胶原蛋白是细胞外基质最重要的成分之一，参与组织的强度，细胞粘附和细胞增殖。几种胶原蛋白和翻译后修饰酶基因的突变会导致Ehlers-Danlos综合征（EDS），其特征是关节和皮肤超伸以及各种器官的脆弱性。碳水化合物磺基转移酶14 /皮肤素4 - O-磺基转移酶-1（CHST14 / D4ST1）是生物合成皮肤素硫酸盐的关键酶，硫酸皮肤素是各种蛋白聚糖的侧链，包括双糖聚糖，可通过它们的相互作用调节胶原蛋白原纤维。发现CHST14中的突变会引起一种新形式的EDS，称为肌肉收缩型EDS（mcEDS- CHST14）。大型皮下血肿是最严重的并发症之一，伴有生活质量下降和潜在致死率。在这项研究中，Chst14基因缺失的小鼠有望成为mcEDS- CHST14血管异常的动物模型。但是，由于大多数Chst14基因缺失的纯合子（Chst14 ^-/-）小鼠的围生期致死性，只产生了数量有限的成年小鼠。因此，我们调查了这些胎儿的胎盘。Chst14的胎盘^-/-胎儿体重减轻，血管结构改变，缺血和/或坏死样改变。电子显微镜显示胎盘绒毛中毛细血管基底膜结构异常。这些发现表明Chst14对胎盘血管发育和胎儿围产期生存至关重要。此外，Chst14 ^-/-胎儿的胎盘可能是mcEDS- CHST14血管表现（例如大的皮下血肿）的有用模型。