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Developmental abnormalities in cultured mouse embryos deprived of retinoic by inhibition of yolk-sac retinol binding protein synthesis.

机译:通过抑制卵黄囊视黄醇结合蛋白合成,剥夺了视黄酸的小鼠胚胎发育异常。

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摘要

Presomitic and 3- to 12-somite pair cultured mouse embryos were deprived of retinoic acid (RA) by yolk-sac injections of antisense oligodeoxynucleotides for retinol binding protein (RBP). Inhibition of yolk-sac RBP synthesis was verified by immunohistochemistry, and the loss of activity of a lacZ-coupled RA-sensitive promoter demonstrated that embryos rapidly became RA-deficient. This deficiency resulted in malformations of the vitelline vessels, cranial neural tube, and eye, depending upon the stage of embryonic development at the time of antisense injection. Addition of RA to the culture medium at the time of antisense injection restored normal development implicating the role of RBP in embryonic RA synthesis. Furthermore, the induced RA deficiency resulted in early down-regulation of developmentally important genes including TGF-beta1 and Shh.
机译:通过卵黄囊注射视黄醇结合蛋白(RBP)的反义寡脱氧核苷酸,剥夺了成年和3至12至12个成对配对的小鼠胚胎的视黄酸(RA)。卵黄囊RBP合成的抑制作用已通过免疫组织化学验证,并且lacZ偶联的RA敏感启动子的活性丧失表明胚胎迅速变为RA缺陷型。这种缺陷导致卵黄血管,颅神经管和眼畸形,具体取决于反义注射时胚胎发育的阶段。反义注射时在培养基中添加RA可恢复正常发育,这牵涉RBP在胚胎RA合成中的作用。此外,诱发的RA缺乏导致早期重要的发育基因TGF-beta1和Shh下调。

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