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Peri-Implantation Lethality in Mice Lacking the Sm Motif-Containing Protein Lsm4

机译：缺少Sm基序蛋白Lsm4的小鼠的围着床致死率

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摘要

Small nuclear ribonucleoproteins (snRNPs) are particles present only in eukaryotic cells. They are involved in a large variety of RNA maturation processes, most notably in pre-mRNA splicing. Several of the proteins typically found in snRNPs contain a sequence signature, the Sm domain, conserved from yeast to mammals. By using a promoter trap strategy to target actively transcribed loci in murine embryonic stem cells, a new murine gene encoding an Sm motif-containing protein was identified. Database searches revealed that it is the mouse orthologue of Lsm4p, a protein found in yeast and human cells and putatively associated with U6 snRNA. Introduction of the geo reporter gene cassette under the control of the murine Lsm4(mLsm4) endogenous promoter showed that the gene was ubiquitously transcribed in embryonic and adult tissues. The insertion of the geo cassette disrupted the mLsm4 allele, and homozygosity for the mutation led to a recessive embryonic lethal phenotype. mLsm4-null zygotes survived to the blastocyst stages, implanted into the uterus, but died shortly thereafter. The early death of mLsm4p-null mice suggests that the role of mLsm4p in splicing is essential and cannot be compensated by other Lsm proteins.
机译：小核糖核蛋白（snRNPs）是仅存在于真核细胞中的颗粒。它们参与各种各样的RNA成熟过程，最显着的是mRNA前剪接。通常在snRNPs中发现的几种蛋白质包含从酵母到哺乳动物保守的序列签名Sm域。通过使用启动子陷阱策略来靶向在小鼠胚胎干细胞中主动转录的基因座，鉴定了一种新的编码含Sm基序蛋白的小鼠基因。数据库搜索显示它是Lsm4p的小鼠直系同源物，Lsm4p是一种在酵母和人细胞中发现的蛋白，推测与U6 snRNA相关。在小鼠 Lsm4 （ mLsm4 ）内源启动子的控制下引入 geo 报告基因盒，表明该基因在胚胎和生殖细胞中普遍存在。成人组织。插入 geo 盒破坏了 mLsm4 等位基因，纯合突变导致隐性胚胎致死表型。 mLsm4无受精卵存活到胚泡阶段，植入子宫，但此后不久死亡。 mLsm4p-null小鼠的早期死亡提示，mLsm4p在剪接中的作用至关重要，不能被其他Lsm蛋白补偿。

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