Hypomorphic mutation in hnRNP U results in post-implantation lethality
Hypomorphic mutation in hnRNP U results in post-implantation lethality
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DOI：
10.1007/s11248-004-8147-8
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发表时间：
2005-04-01
影响因子：
3
通讯作者：
Ruley, HE
中科院分区：
文献类型：
--
作者：
Roshon, MJ;Ruley, HE
本研究的特点是胚胎致死突变诱导插入U3Neo基因陷阱逆转录病毒的基因编码的异质性核糖核蛋白U（Hnrnpu），它映射到小鼠1号染色体的远端臂的内含子。发现小鼠hnRNP U在341个氨基酸残基中除了一个之外与人蛋白质完全相同。原病毒纯合子胚胎在发育6.5天后（E6.5）表现出明显的异常，并被E10.5吸收。插入的新霉素抗性基因的表达涉及对位于新霉素抗性基因中的隐蔽的3'剪接位点的选择性剪接，导致低构象突变。从植入前胚泡分离的纯合突变细胞系表达的hnRNP U转录物水平比野生型细胞低2至5倍，表明胚胎发育需要接近野生型水平的hnRNP U。
The present study characterized an embryonic lethal mutation induced by insertion of the U3Neo gene trap retrovirus into an intron of the gene encoding heterogeneous ribonuclear protein U (Hnrnpu), which maps to the distal arm of mouse chromosome 1. Murine hnRNP U was found to be identical to the human protein at all but one of 341 amino acid residues. Embryos homozygous for the provirus showed obvious abnormalities after 6.5 days of development (E6.5) and were resorbed by E10.5. Expression of the inserted neomycin-resistance gene involved alternative splicing to a cryptic 3' splice site located in the neomycin resistance gene resulting in a hypomorpbic mutation. Homozygous mutant cell lines isolated from preimplantation blastocysts expressed hnRNP U transcripts at levels 2 to 5 times lower than wildtype cells, suggesting that nearly wild-type levels of hnRNP U Are required for embryonic development.