Cloning of inv, a gene that controls left/right asymmetry and kidney development
Cloning of inv, a gene that controls left/right asymmetry and kidney development
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DOI：
10.1038/26006
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发表时间：
1998-09-10
期刊：
影响因子：
64.8
通讯作者：
Yokoyama, T
中科院分区：
文献类型：
--
作者：
Mochizuki, T;Saijoh, Y;Yokoyama, T
大多数脊椎动物的内脏都表现出明显的左右不对称。小鼠胚胎转向反转（inv）突变先前是通过随机插入突变(1)产生的；它会产生左/右极性的持续逆转（反位）和肾脏囊肿的形成(2)。在inv突变体中，nodal和left基因的不对称表达模式被逆转（3-6），表明inv可能在左/右决定的早期起作用。在这里，我们发现了一个位于内位的新基因。编码的蛋白在其氨基端含有Ank/Swi6基序（7,8）的15个连续重复序列。在成人组织中，该基因在肾脏和肝脏中的表达最高，在前体细胞阶段的胚胎中也可见到。对转基因基因组和候选基因结构的分析表明，候选基因是唯一被破坏的基因。转基因引入编码候选蛋白的小基因恢复了inv突变体正常的左/右不对称和肾脏发育，确认了候选基因的身份。
Most vertebrate internal organs show a distinctive left/right asymmetry. The inv (inversion of embryonic turning) mutation in mice was created previously by random insertional mutagenesis(1); it produces both a constant reversal of left/right polarity (situs inversus) and cyst formation in the kidneys(2). Asymmetric expression patterns of the genes nodal and lefty are reversed in the inv mutant(3-6), indicating that inv may act early in left/right determination. Here we identify a new gene located at the inv locus. The encoded protein contains 15 consecutive repeats of an Ank/Swi6 motif(7,8) at its amino terminus. Expression of the gene is the highest in the kidneys and liver among adult tissues, and is seen in presomite-stage embryos. Analysis of the transgenic genome and the structure of the candidate gene indicate that the candidate gene is the only gene that is disrupted in inv mutants. Transgenic introduction of a minigene encoding the candidate protein restores normal left/right asymmetry and kidney development in the inv mutant, confirming the identity of the candidate gene.