Characterization of chromosomal inversion of the mouse hairy ears (Eh) mutation associated with cleft palate
Characterization of chromosomal inversion of the mouse hairy ears (Eh) mutation associated with cleft palate
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DOI：
10.1007/s00335-007-9015-7
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发表时间：
2007-04-01
期刊：
影响因子：
2.5
通讯作者：
Kunieda, Tetsuo
中科院分区：
文献类型：
--
作者：
Katayama, Kentaro;Furuno, Aki;Kunieda, Tetsuo
小鼠毛耳（Eh）突变起源于中子辐照实验，与15号染色体倒位有关。Eh/+小鼠耳廓较小，耳廓上有多余的毛发，但Eh/Eh小鼠的表型特征尚不清楚。在这项研究中，我们发现 Eh/Eh 小鼠在出生后不久就死亡，并且由于腭架生长受损而导致腭裂。由于位于倒位断点上的基因可能与染色体倒位相关的缺陷有关，因此我们确定了 Eh 倒位的断点。我们使用了一种新的遗传方法，该方法使用两个重叠倒位之间交叉产生的重组染色体来确定断点。 Koa 是一种与 15 号染色体倒位相关的小鼠突变，与 Eh 倒位部分重叠。我们制作了Eh +/+ Koa双杂合子，并获得了具有两个倒位断点两侧区域的缺失和重复的重组染色体，这是通过在这些倒位的重叠区域内交叉产生的。通过定义删除的区域，我们确定了 Eh 反转的断点。然后，我们检查了断点附近基因的表达，发现Eh/Eh小鼠发育中的腭中存在Hoxc5基因和功能未知的转录物的异位表达，这可能是腭裂的原因。
The hairy ears (Eh) mutation in the mouse originated from neutron irradiation experiments and is associated with chromosomal inversion on chromosome 15. Eh/+ mice have small pinna and extra hairs on the pinna but the phenotypic features of Eh/Eh mice are unclear. In this study we found that Eh/Eh mice died shortly after birth and had a cleft palate caused by impaired growth of palate shelves. Because genes located on the breakpoints of inversion are likely to be responsible for the defects associated with chromosomal inversions, we determined the breakpoints of the Eh inversion. We used a new genetic method that uses recombinant chromosomes resulting from crossing over between two overlapping inversions to determine the breakpoints. Koa is a mouse mutation associated with inversion of chromosome 15, which partially overlaps with the Eh inversion. We made Eh +/+ Koa double heterozygotes and obtained the recombinant chromosomes possessing deletion and duplication of the regions flanked by the breakpoints of both inversions, which were generated by crossing over within the overlapped region of these inversions. By defining the deleted regions we identified the breakpoints of the Eh inversion. We then examined the expression of genes in the vicinities of the breakpoints and found ectopic expression of the Hoxc5 gene and a transcript with unknown function in the developing palate of Eh/Eh mice, which is likely to be responsible for the cleft palate.