A phenotype-based screen for embryonic lethal mutations in the mouse
A phenotype-based screen for embryonic lethal mutations in the mouse
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DOI：
10.1073/pnas.95.13.7485
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发表时间：
1998-06-23
影响因子：
11.1
通讯作者：
Anderson, KV
中科院分区：
文献类型：
--
作者：
Kasarskis, A;Manova, K;Anderson, KV
控制早期哺乳动物胚胎发育的遗传途径仍然知之甚少，部分原因是系统突变筛选在果蝇、秀丽隐杆线虫和斑马鱼中指导胚胎发育的基因和途径的鉴定中非常成功，但尚未应用于哺乳动物胚胎发生。在这里，我们证明乙基亚硝基脲的化学诱变可以与 小鼠基因组学资源，用于识别哺乳动物胚胎发生所必需的新基因。对妊娠中期胚胎异常形态表型的初步筛选确定了五个突变系；其中四个品系的表型是由映射到基因组单个区域的隐性性状引起的。三种突变株系显示出神经管闭合缺陷：一种是由开放蛋白（opb）基因座的等位基因引起的，一种定义了先前未知的基因座，另一种具有复杂的遗传基础。两种突变产生了新的早期表型，并映射到先前未涉及胚胎模式的基因组区域。
The genetic pathways that control development of the early mammalian embryo have remained poorly understood, in part because the systematic mutant screens that have been so successful in the identification of genes and pathways that direct embryonic development in Drosophila, Caenorhabditis elegans, and zebrafish have not been applied to mammalian embryogenesis, Here we demonstrate that chemical mutagenesis with ethylnitrosourea can be combined with the resources of mouse genomics to identify new genes that are essential for mammalian embryogenesis. A pilot screen for abnormal morphological phenotypes of midgestation embryos identified five mutant lines; the phenotypes of four of the lines are caused by recessive traits that map to single regions of the genome. Three mutant lines display defects in neural tube closure: one is caused by an allele of the open bl ain (opb) locus, one defines a previously unknown locus, and one has a complex genetic basis. Two mutations produce novel early phenotypes and map to regions of the genome not previously implicated in embryonic patterning.