TARGETED DISRUPTION OF THE EVEN-SKIPPED GENE, EVX1, CAUSES EARLY POSTIMPLANTATION LETHALITY OF THE MOUSE CONCEPTUS

被引:86
作者
SPYROPOULOS, DD [1 ]
CAPECCHI, MR [1 ]
机构
[1] UNIV UTAH,SCH MED,HOWARD HUGHES MED INST,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112
关键词
EVX1; EVEN-SKIPPED; HOMEO BOX GENE; CONCEPTUS; TROPHECTODERM; VISCERAL ENDODERM; EGG CYLINDER; BLASTOCYST OUTGROWTH; POSTIMPLANTATION MUTANT;
D O I
10.1101/gad.8.16.1949
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Implantation within the mammalian uterus elicits dramatic changes in the growth, differentiation, and morphogenesis of the conceptus. This process is interrupted in mice carrying a targeted disruption of the murine evx1 gene, a homolog of the Drosophila even-skipped (eve) gene. Upon implantation, presumptive evx1(-) homozygotes elicit a decidual response, invade the uterine-epithelium, and attach to the basement membrane between uterine stroma and epithelium, but fail to differentiate extraembryonic tissues or to form egg cylinders prior to resorption. Retrograde analysis of embryo genotypes demonstrates that homozygotes could be isolated as free-floating blastocysts but not as gastrulating egg cylinders. Homozygous mutant blastocysts appeared normal and, when grown in vitro, attach, proliferate, and form trophoblastic giant cells surrounding a growing inner cell mass before rapidly degenerating. In situ hybridization analysis demonstrates evx1 gene expression within the visceral endoderm after implantation and prior to gastrulation, at a time in which the mutant phenotype is first detected.
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页码:1949 / 1961
页数:13
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