Expression of Key Genes of UPR in Normal and Abnormal Limb Development during Mouse Embryogenesis

BACKGROUND AND AIM:To study the expression of the key genes in UPR,which are Atf6,Ire1,Perk and Grp78,in normal forelimb and short forelimb formations during mouse embryogenesis.MATERIALS AND METHODS:On gestational day 10(GD10),the pregnant mice of the treatment group were fed with 80 mg/kg all-trans retinoic acid,and those of the control group received same volume of soybean oil.The forelimbs of all embryos were harvested during GD11-GD18,and the expression levels of Atf6,Ire1,Perk and Grp78 in all samples were measured by real-time quantity reverse transcript polymerase chain reaction(QRT-PCR).RESULTS:Except Ire1 that was not expressed on GD18,the key genes of UPR were all expressed in the normal limbs during GD11-GD18,and there were two expression peaks around GD13 and GD17.In the normal limbs,the expression of Grp78 was highest and that of Ire1 was lowest,and the difference was so obviously.Before GD15,the expressions of Atf6,Ire1,Perk and Grp78 in the abnormal forelimbs were higher than those in the normal limbs,and after GD15,the expression of these four genes in the abnormal forelimbs were lower than those in the normal limbs,and was relatively stable at a low level.In the abnormal limbs,there was a very obvious expression peak of all genes between GD12-GD14;the time course was longer and the expression of this peak was higher than that of the normal limbs.CONCLUSION:During mouse embryogenesis,the expression abundance of key genes of UPR in all-trans retinoic acid-induced short limb malformations was obviously increased during GD11-GD14,and was suppressed during GD16-GD18,so we think UPR may be teratogenic.