Unraveling the role of Xist in X chromosome inactivation: insights from rabbit model and deletion analysis of exons and repeat A

X chromosome inactivation (XCI) is a dosage compensation process that aims to equalize the expression of X-linked genes between males and females. Initiation of XCI relies on Xist , which is continuously expressed in somatic cells during XCI maintenance. How Xist impacts XCI maintenance remains unclear, and its functional motifs remain unclear. In this study, we conducted a comprehensive analysis of the Xist . The results demonstrate that rabbits serve as an ideal non-primate animal model for investigating the functions of Xist in vivo. And homozygous knockout of exon 1, exon 6 and repeat A in females resulted in embryonic lethality. However, XΔReAX females with Xist expression from the intact X chromosome, did not display any abnormalities. Interestingly, there were no significant differences between females with homozygous knockout of exons 2-5 and wild-type rabbits. This suggests that exons 2, 3, 4, and 5 of Xist are less important for XCI. These insights provide valuable knowledge about the functional mechanism of Xist .