A NULL C-MYC MUTATION CAUSES LETHALITY BEFORE 10.5 DAYS OF GESTATION IN HOMOZYGOTES AND REDUCED FERTILITY IN HETEROZYGOUS FEMALE MICE
A NULL C-MYC MUTATION CAUSES LETHALITY BEFORE 10.5 DAYS OF GESTATION IN HOMOZYGOTES AND REDUCED FERTILITY IN HETEROZYGOUS FEMALE MICE
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DOI：
10.1101/gad.7.4.671
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发表时间：
1993-04-01
影响因子：
10.5
通讯作者：
BRADLEY, A
中科院分区：
文献类型：
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作者：
DAVIS, AC;WIMS, M;BRADLEY, A
为了直接评估c-myc在细胞增殖、分化和胚胎发生中的功能，我们在胚胎干细胞中使用同源重组来产生杂合和纯合c-myc突变ES细胞系。该突变在蛋白质水平上是无效等位基因。来自7个杂合细胞系的小鼠嵌合体将突变等位基因传递给它们的后代。对来自两个克隆的胚胎的分析表明，在妊娠9.5至10.5天的纯合子中，突变是致命的。与同窝仔相比，胚胎通常较小，发育迟缓。病理异常包括心脏、心包、神经管和胚胎发育延迟或失败。杂合子雌性在妊娠9.5天前由于胚胎吸收而降低了生育力，14%的植入胚胎。c-Myc蛋白对于妊娠10.5天以上的胚胎存活是必需的;然而，它似乎在ES细胞系和在该时间之前的胚胎中的细胞分裂中都被抑制。
To directly assess c-myc function in cellular proliferation, differentiation, and embryogenesis, we have used homologous recombination in embryonic stem cells to generate both heterozygous and homozygous c-myc mutant ES cell lines. The mutation is a null allele at the protein level. Mouse chimeras from seven heterozygous cell lines transmitted the mutant allele to their offspring. The analysis of embryos from two clones has shown that the mutation is lethal in homozygotes between 9.5 and 10.5 days of gestation. The embryos are generally smaller and retarded in development compared with their littermates. Pathologic abnormalities include the heart, pericardium, neural tube, and delay or failure in turning of the embryo. Heterozygous females have reduced fertility owing to embryonic resorption before 9.5 days of gestation in 14% of implanted embryos. c-Myc protein is necessary for embryonic survival beyond 10.5 days of gestation; however, it appears to be dispensable for cell division both in ES cell lines and in the the embryo before that time.