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一个X连锁的HMG-lacZ转基因在小鼠胚胎中的表达:染色体印记和谱系特异性X染色体活性的意义。

Expression of an X-linked HMG-lacZ transgene in mouse embryos: implication of chromosomal imprinting and lineage-specific X-chromosome activity.

作者信息

Tam P P, Williams E A, Tan S S

机构信息

Embryology Unit, Children's Medical Research Institute, Wentworthville NSW, Australia.

出版信息

Dev Genet. 1994;15(6):491-503. doi: 10.1002/dvg.1020150608.

DOI:10.1002/dvg.1020150608
PMID:7834909
Abstract

X-chromosome activity in female mouse embryos was studied at the cellular level using an X-linked lacZ transgene which encodes beta-galactosidase (beta-Gal). Translation of maternal RNA in oocytes is seen as beta-Gal activity that persists into early cleavage-stages. Zygotic transcription of the transgene from the maternal X chromosome (Xm) is first found at about the 8-cell stage. By contrast, expression of the lacZ transgene on the paternal X chromosome (Xp) is not seen until later at the 16-32-cell stage. Preferential inactivation of Xp occurs in the mural trophectoderm, the primitive endoderm, and derivatives of the polar trophectoderm, but a small number of cells in these lineages may still retain an active paternal X chromosome. X inactivation begins at 3.5 days in the inner cell mass but contrary to previous findings the process is not completed in the embryonic ectoderm by 5.5 to 6.0 days. Regional variation in beta-Gal activity is also observed in the embryonic ectoderm during gastrulation which may be related to the specification of cell fates. Random inactivation of Xp and Xm ensues in all somatic tissues but the process is completed at different times in different tissues. The slower progression of X inactivation in tissues such as the notochord, the heart, and the embryonic gut is primarily due to the persistent maintenance of two active X chromosomes in a significant fraction of cells in these tissues. Recent findings on the methylation of endogenous X-linked genes suggest that the prolonged expression of beta-Gal might also be due to the different rate of spreading of inactivation along the X chromosome to the lacZ transgene locus in different tissues.

摘要

利用编码β-半乳糖苷酶(β-Gal)的X连锁lacZ转基因,在细胞水平上研究了雌性小鼠胚胎中的X染色体活性。卵母细胞中母源RNA的翻译表现为持续到早期卵裂阶段的β-Gal活性。母源X染色体(Xm)上转基因的合子转录最早在约8细胞阶段被发现。相比之下,父源X染色体(Xp)上lacZ转基因的表达直到后来的16 - 32细胞阶段才可见。Xp在壁滋养外胚层、原始内胚层和极滋养外胚层的衍生物中优先失活,但这些谱系中的少数细胞可能仍保留活跃的父源X染色体。X失活在3.5天时在内细胞团中开始,但与先前的发现相反,该过程在5.5至6.0天时在胚胎外胚层中并未完成。在原肠胚形成过程中,胚胎外胚层中也观察到β-Gal活性的区域差异,这可能与细胞命运的特化有关。Xp和Xm在所有体细胞组织中随机失活,但该过程在不同组织中于不同时间完成。在脊索、心脏和胚胎肠道等组织中,X失活进展较慢主要是由于这些组织中相当一部分细胞持续维持两条活跃的X染色体。关于内源性X连锁基因甲基化的最新发现表明,β-Gal的延长表达也可能是由于失活沿X染色体向lacZ转基因位点在不同组织中传播的速率不同。

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Expression of an X-linked HMG-lacZ transgene in mouse embryos: implication of chromosomal imprinting and lineage-specific X-chromosome activity.一个X连锁的HMG-lacZ转基因在小鼠胚胎中的表达:染色体印记和谱系特异性X染色体活性的意义。
Dev Genet. 1994;15(6):491-503. doi: 10.1002/dvg.1020150608.
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