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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development
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Filamin B deficiency in mice results in skeletal malformations and impaired microvascular development

机译：小鼠纤维蛋白B缺乏症会导致骨骼畸形和微血管发育受损

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摘要

Mutations in filamin B (FLNB). a gene encoding a cytoplasmic actin-binding protein, have been found in human skeletal disorders, including boomerang dysplasia, spondylocarpotarsal syndrome, Larsen syndrome, and atelosteogenesis phenotypes Ⅰ and Ⅲ. To examine the role of FLNB in vivo, we generated mice with a targeted disruption of Flnb. Fewer than 3% of homozygous embryos reached term, indicating that Flnb is important in embryonic development. Heterozygous mutant mice were indistinguishable from their wild-type siblings. Flnb was ubiquitously expressed; strong expression was found in endothelial cells and chondrocytes. Flnb-deficient fibroblasts exhibited more disorganized formation of actin filaments and reduced ability to migrate compared with wild-type controls. Flnb-deficient embryos exhibited impaired development of the microvasculature and skeletal system. The few Flnb-deficient mice that were born were very small and had severe skeletal malformations, including scoliotic and kyphotic spines, lack of intervertebral discs, fusion of vertebral bodies, and reduced hyaline matrix in extremities, thorax, and vertebrae. These mice died or had to be euthanized before 4 weeks of age. Thus, the phenotypes of Flnb-deficient mice closely resemble those of human skeletal disorders with mutations in FLNB.
机译：丝蛋白B（FLNB）中的突变。在人骨骼疾病中发现了一种编码细胞质肌动蛋白结合蛋白的基因，包括回旋镖发育不良，脊椎腕骨综合征，拉森综合征以及成骨性表型Ⅰ和Ⅲ。为了检查FLNB在体内的作用，我们产生了具有针对性破坏Flnb的小鼠。只有不到3％的纯合子胚胎达到足月期，表明Flnb在胚胎发育中很重要。杂合突变小鼠与野生型同胞没有区别。 Flnb被普遍表达；在内皮细胞和软骨细胞中发现强表达。与野生型对照相比，缺乏Flnb的成纤维细胞表现出更多的肌动蛋白丝变形，并且迁移能力降低。 Flnb缺乏的胚胎表现出微脉管系统和骨骼系统发育受损。出生的少数Flnb缺陷小鼠非常小，并且具有严重的骨骼畸形，包括脊柱侧凸和后凸脊柱，椎间盘缺乏，椎体融合以及四肢，胸部和椎骨的透明质矩阵减少。这些小鼠在4周龄之前死亡或必须被安乐死。因此，缺乏Flnb的小鼠的表型非常类似于具有FLNB突变的人骨骼疾病的表型。

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