ECTOPIC EXPRESSION OF THE H19 GENE IN MICE CAUSES PRENATAL LETHALITY

被引:159
作者
BRUNKOW, ME
TILGHMAN, SM
机构
[1] PRINCETON UNIV,HOWARD HUGHES MED INST,PRINCETON,NJ 08544
[2] PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544
关键词
H19; GENE; MOUSE EMBRYO; ECTOPIC EXPRESSION; TRANSGENIC EXPRESSION;
D O I
10.1101/gad.5.6.1092
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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页码:1092 / 1101
页数:10
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