Radiographic analysis of zebrafish skeletal defects
Radiographic analysis of zebrafish skeletal defects
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DOI：
10.1016/s0012-1606(03)00399-3
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发表时间：
2003-12-01
影响因子：
2.7
通讯作者：
Halpern, ME
中科院分区：
文献类型：
--
作者：
Fisher, S;Jagadeeswaran, P;Halpern, ME
在模式脊椎动物中系统识别骨骼发育不良有助于深入了解人类骨骼疾病的发病机制，并有助于鉴定人类同源基因。我们正在对成年斑马鱼的骨骼发育不良进行突变筛选，使用放射照相技术来检测骨骼解剖和骨骼形态的异常。我们分离了吉娃娃，这是一种导致骨骼生长普遍缺陷的显性突变。杂合吉娃娃鱼在表型上与人类成骨不全有相似之处，成骨不全是一种由I型胶原基因突变引起的骨骼发育不良。吉娃娃突变的定位和分子特征表明，缺陷存在于编码I型胶原(α1)链的基因中。因此，吉娃娃在生物和分子水平上准确地模拟了成骨不全，并将被证明是疾病病理生理学研究的重要资源。射线照相是一种实用的筛查工具，可以检测成年斑马鱼的细微骨骼异常。吉娃娃的鉴定表明，将发现类似于人类骨骼发育不良的突变表型。(C)2003 Elsevier Inc.保留所有权利。
Systematic identification of skeletal dysplasias in model vertebrates provides insight into the pathogenesis of human skeletal disorders and can aid in the identification of orthologous human genes. We are undertaking a mutagenesis screen for skeletal dysplasias in adult zebrafish, using radiography to detect abnormalities in skeletal anatomy and bone morphology. We have isolated chihuahua, a dominant mutation causing a general defect in bone growth. Heterozygous chihuahua fish have phenotypic similarities to human osteogenesis imperfecta, a skeletal dysplasia caused by mutations in the type I collagen genes. Mapping and molecular characterization of the chihuahua mutation indicates that the defect resides in the gene encoding the collagen I(alpha1) chain. Thus, chihuahua accurately models osteogenesis imperfecta at the biologic and molecular levels, and will prove an important resource for studies on the disease pathophysiology. Radiography is a practical screening tool to detect subtle skeletal abnormalities in the adult zebrafish. The identification of chihuahua demonstrates that mutant phenotypes analogous to human skeletal dysplasias will be discovered. (C) 2003 Elsevier Inc. All rights reserved.