Transgenic mdx mice expressing dystrophin with a deletion in the actin-binding domain display a "mild Becker" phenotype.
Transgenic mdx mice expressing dystrophin with a deletion in the actin-binding domain display a "mild Becker" phenotype.
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在肌动蛋白结合结构域中表达肌营养不良蛋白的转基因MDX小鼠表现出“轻度贝克”表型。
DOI：
10.1083/jcb.134.4.873
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发表时间：
1996-08
影响因子：
7.8
通讯作者：
Chamberlain, JS
中科院分区：
文献类型：
--
作者：
Corrado, K;Rafael, JA;Mills, PL;Cole, NM;Faulkner, JA;Wang, K;Chamberlain, JS
肌营养不良蛋白的肌动蛋白结合域的功能意义，缺乏在杜氏肌营养不良症患者的蛋白质，仍然难以捉摸。该结构域（结构域I）缺失的患者通常表达低水平的截短蛋白。与这种缺失相关的中度至重度表型是否是由基本功能的丧失或功能蛋白水平的降低引起的尚不清楚。为了解决这个问题，我们已经产生了转基因小鼠，表达野生型水平的肌营养不良蛋白删除的大部分肌动蛋白结合域。转基因衍生的蛋白质缺少氨基酸45-273，去除了3个体外鉴定的肌动蛋白相互作用位点中的2个和铰链1的一部分。在缺乏野生型肌营养不良蛋白（mdx）的小鼠中检查这种缺失的效果表明，功能性结构域I对于预防营养不良表型不是必需的。然而，与中央杆结构域中的缺失和全长肌营养不良蛋白相反，这两者的功能仅为野生型水平的20%，结构域I中缺失的蛋白质必须以高水平表达以防止严重的营养不良。这些结果也与将肌营养不良蛋白连接到细胞外基质的COOH末端结构域的截短导致的严重营养不良形成对比。轻度表型与域I-缺失的小鼠中观察到表明，一个完整的肌动蛋白结合域是不是必不可少的，虽然它有助于肌营养不良蛋白的一个重要功能。这些研究还表明，肌营养不良蛋白和肌膜下细胞骨架之间的联系不仅仅涉及结构域I与肌动蛋白丝的简单连接。
The functional significance of the actin-binding domain of dystrophin, the protein lacking in patients with Duchenne muscular dystrophy, has remained elusive. Patients with deletions of this domain (domain I) typically express low levels of the truncated protein. Whether the moderate to severe phenotypes associated with such deletions result from loss of an essential function, or from reduced levels of a functional protein, is unclear. To address this question, we have generated transgenic mice that express wild-type levels of a dystrophin deleted for the majority of the actin-binding domain. The transgene derived protein lacks amino acids 45-273, removing 2 of 3 in vitro identified actin interacting sites and part of hinge 1. Examination of the effect of this deletion in mice lacking wild-type dystrophin (mdx) suggests that a functional domain I is not essential for prevention of a dystrophic phenotype. However, in contrast to deletions in the central rod domain and to full-length dystrophin, both of which are functional at only 20% of wild-type levels, proteins with a deletion in domain I must be expressed at high levels to prevent a severe dystrophy. These results are also in contrast to the severe dystrophy resulting from truncation of the COOH-terminal domain that links dystrophin to the extracellular matrix. The mild phenotype observed in mice with domain I-deletions indicates that an intact actin-binding domain is not essential, although it does contribute to an important function of dystrophin. These studies also suggest the link between dystrophin and the subsarcolemmal cytoskeleton involves more than a simple attachment of domain I to actin filaments.
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DOI：
10.1083/jcb.122.4.809
发表时间：
1993-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ervasti JM;Campbell KP
通讯作者：
Campbell KP
影响因子：
4.2
作者：
BUSHBY, KMD
通讯作者：
BUSHBY, KMD
影响因子：
3.5
作者：
BONETKERRACHE, A;FABBRIZIO, E;MORNET, D
通讯作者：
MORNET, D
影响因子：
4.8
作者：
JARRETT, HW;FOSTER, JL
通讯作者：
FOSTER, JL
影响因子：
30.8
作者：
COX, GA;SUNADA, Y;CHAMBERLAIN, JS
通讯作者：
CHAMBERLAIN, JS