ECTOPIC EXPRESSION OF THE H19 GENE IN MICE CAUSES PRENATAL LETHALITY
ECTOPIC EXPRESSION OF THE H19 GENE IN MICE CAUSES PRENATAL LETHALITY
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DOI：
10.1101/gad.5.6.1092
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发表时间：
1991-06-01
影响因子：
10.5
通讯作者：
TILGHMAN, SM
中科院分区：
文献类型：
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作者：
BRUNKOW, ME;TILGHMAN, SM
小鼠H19基因在发育中的小鼠胚胎的内胚层和中胚层来源的广泛组织中表达。其表达在出生后不久在除骨骼肌外的所有组织中被抑制。这个基因的不寻常之处在于它可能不编码蛋白质，尽管它在哺乳动物中是保守的。RNA产物在细胞质颗粒中被发现为剪接和多腺苷酸化的RNA。为了探测这个不寻常的基因是否有功能，将多余的拷贝引入小鼠受精卵。转基因后代以非常低的频率获得，但在任何情况下都不表达转基因。基因本身对胚胎有害，这是通过将结构基因的一个突变体导入受精卵而确定的，在该突变体中，其最保守的片段被删除了。转基因创始人以较高的频率获得，这些表达改变的转基因在表达内源性H19基因的组织的子集中以高速率表达。致命影响在妊娠后期，即第14天至出生之间表现出来。
The mouse H19 gene is expressed in a broad array of tissues of both endoderm and mesoderm origin in the developing mouse embryo. Its expression is repressed in all tissues except skeletal muscle shortly after birth. This gene is unusual in that it may not encode a protein, despite its conservation in mammals. The RNA product is found as a spliced and polyadenylated RNA in a cytoplasmic particle. To probe whether this unusual gene is functional, excess copies were introduced into mouse zygotes. Transgenic progeny were obtained at a very low frequency, but in no instance was the transgene expressed. That the gene itself was deleterious to embryos was established by introducing into zygotes a mutant of the structural gene in which its most conserved segment was deleted. Transgenic founders were obtained at a higher frequency, and these expressed the altered transgene at high rates in a subset of the tissues that express the endogenous H19 gene. The lethal effects are manifested late in gestation, between day 14 and birth.