Båvik C, Ward S J, Chambon P
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Instutut National de la Santé et de la Recherche Médicale, Universite Louis Pasteur, C.U. de Strasbourg, France.
Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):3110-4. doi: 10.1073/pnas.93.7.3110.
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.
通过向卵黄囊注射视黄醇结合蛋白（RBP）的反义寡脱氧核苷酸，剥夺前体节以及具有3至12对体节的培养小鼠胚胎中的视黄酸（RA）。通过免疫组织化学验证卵黄囊RBP合成的抑制，并且与lacZ偶联的RA敏感启动子活性的丧失表明胚胎迅速变得RA缺乏。这种缺乏导致卵黄血管、颅神经管和眼睛的畸形，这取决于反义注射时胚胎发育的阶段。在反义注射时向培养基中添加RA可恢复正常发育，这表明RBP在胚胎RA合成中的作用。此外，诱导的RA缺乏导致包括TGF-β1和Shh在内的发育重要基因的早期下调。
