Mutation of an axonemal dynein affects left right asymmetry in inversus viscerum mice
Mutation of an axonemal dynein affects left right asymmetry in inversus viscerum mice
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DOI：
10.1038/40140
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发表时间：
1997-10-30
期刊：
影响因子：
64.8
通讯作者：
Brueckner, M
中科院分区：
文献类型：
--
作者：
Supp, DM;Witte, DP;Brueckner, M
在最初双侧对称的胚胎中，沿着左右（LR）轴的特征性内脏不对称的发展是脊椎动物图案化的基本特征。等位基因小鼠内脏倒位突变（iv）（1，2）和无腿突变（lgl）（3，4）在半数活产纯合子中产生LR倒位或内脏倒位，这表明iv基因产物驱动正确的LR测定，并且在其不存在的情况下，该过程是随机的（2），这些突变为研究LR-手不对称性的发展提供了工具，并提供了人类侧化缺陷的小鼠模型。在分子水平上，nodal（5）和lefty（6）的LR不对称表达模式在iv/iv胚胎中是随机的，表明iv在LR特化的遗传层次中早期起作用。在这里，我们报告了轴丝动力蛋白重链基因左/右动力蛋白（lrd）的定位克隆，该基因在lgl和iv中都发生突变，lrd在胚胎第7.5天的胚胎节中表达，与其在LR发育中的作用一致（7）。我们的研究结果表明，动力蛋白，微管为基础的电机，参与决定LR手的不对称性，并提供深入了解这一过程的早期分子机制。
The development of characteristic visceral asymmetries along the left-right (LR) axis in an initially bilaterally symmetrical embryo is an essential feature of vertebrate patterning. The allelic mouse mutations inversus viscerum (iv)(1,2) and legless (lgl)(3,4) produce LR inversion, or situs inversus, in half of live-born homozygotes, This suggests that the iv gene product drives correct LR determination, and in its absence this process is randomized(2), These mutations provide tools for studying the development of LR-handed asymmetry and provide mouse models of human lateralization defects. At the molecular level, the normally LR asymmetric expression patterns of nodal(5) and lefty(6) are randomized in iv/iv embryos, suggesting that iv functions early in the genetic hierarchy of LR specification, Here we report the positional cloning of an axonemal dynein heavy-chain gene, left/right-dynein (lrd), that is mutated in both lgl and iv, lrd is expressed in the node of the embryo at embryonic day 7.5, consistent with its having a role in LR development(7). Our findings indicate that dynein, a microtubule-based motor, is involved in the determination of LR-handed asymmetry and provide insight into the early molecular mechanisms of this process.