Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis
Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis
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DOI：
10.1038/ng1319
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发表时间：
2004-04-01
期刊：
影响因子：
30.8
通讯作者：
Cohn, DH
中科院分区：
文献类型：
--
作者：
Krakow, D;Robertson, SP;Cohn, DH
丝状蛋白是细胞质蛋白，通过将肌动蛋白交联成三维网络来调节细胞骨架的结构和活性，将细胞膜连接到细胞骨架上，并作为细胞内信号传导和蛋白质运输途径的支架（参考文献综述）。1、2）。我们在四种人类骨骼疾病中发现了编码细丝蛋白B的基因突变。我们发现纯合性或复合杂合性的终止密码子突变常染色体隐性脊柱腕跗综合征（SCT，OMIM 272460）和错义突变的个体常染色体显性拉森综合征（OMIM 150250）和围产期致死性骨发育不全I和III表型（AOI，OMIM 108720; AOIII，OMIM 108721）。我们发现细丝蛋白B在人生长板软骨细胞和小鼠发育中的椎体中表达。这些数据表明，这种普遍表达的细胞骨架蛋白在椎骨分割，关节形成和软骨内骨化中具有意想不到的作用。
The filamins are cytoplasmic proteins that regulate the structure and activity of the cytoskeleton by cross-linking actin into three-dimensional networks, linking the cell membrane to the cytoskeleton and serving as scaffolds on which intracellular signaling and protein trafficking pathways are organized (reviewed in refs. 1,2). We identified mutations in the gene encoding filamin B in four human skeletal disorders. We found homozygosity or compound heterozygosity with respect to stop-codon mutations in autosomal recessive spondylocarpotarsal syndrome (SCT, OMIM 272460) and missense mutations in individuals with autosomal dominant Larsen syndrome (OMIM 150250) and the perinatal lethal atelosteogenesis I and III phenotypes (AOI, OMIM 108720; AOIII, OMIM 108721). We found that filamin B is expressed in human growth plate chondrocytes and in the developing vertebral bodies in the mouse. These data indicate an unexpected role in vertebral segmentation, joint formation and endochondral ossification for this ubiquitously expressed cytoskeletal protein.