...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Deletion of the Fanconi Anemia C Gene in Mice Leads to Skeletal Anomalies and Defective Bone Mineralization and Microarchitecture
【24h】

Deletion of the Fanconi Anemia C Gene in Mice Leads to Skeletal Anomalies and Defective Bone Mineralization and Microarchitecture

机译：小鼠中贫血C基因的缺失导致骨骼异常和骨质矿化和微体系结构有缺陷

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

ABSTRACT Fanconi anemia (FA) is a rare genetic disorder associated with a progressive decline in hematopoietic stem cells leading to bone marrow failure. FA is also characterized by a variety of developmental defects including short stature and skeletal malformations. More than half of children affected with FA have radial‐ray abnormalities, and many patients have early onset osteopenia/osteoporosis. Although many Fanconi anemia genes have been identified and a molecular pathway defined, the underlying mechanism leading to bone defects remains elusive. To understand the role of FA genes in skeletal development and bone microarchitecture, we evaluated bone physiology during embryogenesis and in adult FancA ‐ and FancC ‐deficient mice. We found that both FancA ‐/‐ and FancC ‐/‐ embryos have abnormal skeletal development shown by skeletal malformations, growth delay, and reduced bone mineralization. FancC ‐/‐ adult mice present altered bone morphology and microarchitecture with a significant decrease in cortical bone mineral density in a sex‐specific manner. Mechanical testing revealed that male but not female FancC ‐/‐ mice show reduced bone strength compared with their wild‐type littermates. Ex vivo cultures showed that FancA ‐/‐ and FancC ‐/‐ bone marrow–derived mesenchymal stem cells ( BM MSC) have impaired differentiation capabilities together with altered gene expression profiles. Our results suggest that defective bone physiology in FA occurs in utero and possibly results from altered BM MSC function. These results provide valuable insights into the mechanism involved in FA skeletal defects. ? 2018 American Society for Bone and Mineral Research.
机译：摘要FANCONI贫血（FA）是一种罕见的遗传障碍，其造血干细胞的渐进下降导致骨髓衰竭。 FA的特征还在于各种发育缺陷，包括矮小的身材和骨骼畸形。患有FA影响的一半以上的儿童具有径向射线异常，许多患者早期发病骨质增长/骨质疏松症。虽然已经鉴定了许多FANCONI贫血基因并定义了分子途径，但导致骨缺陷的潜在机制仍然难以捉摸。为了了解FA基因在骨骼发育和骨微体系结构中的作用，我们在胚胎发生过程中评估了骨骼生理学和成人Fanca - 和Fancc -DeficioRical。我们发现，Fanca - / - 和Fancc - / - / - 胚胎具有骨骼畸形，生长延迟和骨矿化降低的异常骨骼发育。 FANCC - / - 成人小鼠存在改变的骨形态和微体系结构，以性别特异性方式显着降低皮质骨密度。机械测试显示，男性但不是雌性FANCC - / - 与其野生型凋落物相比，骨骼强度降低。前体内培养表明，FANCA - / - 和FANCC - / - 骨髓衍生的间充质干细胞（BM MSC）与改变的基因表达谱一起具有损害的分化能力。我们的研究结果表明，在子宫内发生FA的骨生理学缺陷，可能是由改变的BM MSC功能产生的。这些结果提供了对FA骨骼缺陷所涉及的机制的有价值的见解。还2018年美国骨骼和矿物学研究。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号