前期研究显示CUL4B丧失功能突变导致X连锁智力低下综合征，患者除智力低下外，还伴有身材矮小、性腺机能减退、肥胖以及外周血中单核细胞增多等症状，提示CUL4B在多种组织的发育中发挥重要作用。利用小鼠模型研究发现CUL4B在胚胎发育、神经系统发育、雄性生殖细胞发育、髓系细胞分化、脂肪细胞分化、胰岛delta细胞发育等过程中发挥重要作用。我们前期发现两种缺失Cul4b基因的雌性小鼠不能生育子代，提示CUL4B在调控雌性生殖细胞和/或早期胚胎发育中发挥重要作用。为此，本课题将利用3种在不同发育时期表达Cre酶的转基因小鼠与我们前期建立的Cul4b flox小鼠交配，获得在卵母细胞发育不同时期敲除Cul4b基因的小鼠，分析在卵母细胞发育不同时期缺失CUL4B对小鼠生育率、卵母细胞发育、早期胚胎发育的影响及其机制。这些研究结果不仅能揭示Cul4b基因的新功能，而且能扩宽对卵母细胞发育异常机制的认识。

Previous studies shown that loss of function mutations in CUL4B gene cause X-linked mental retardation syndrome associated with short stature, hypogonadism, obesity and increased monocytes in peripheral blood, suggesting that CUL4B plays important roles in the development of various tissues. Research using mouse models found that CUL4B played important roles in embryonic development, nervous system development, male germ cell development, myeloid cell differentiation, adipocyte differentiation and pancreatic delta cell development. We have previously found that two strains of female mice lacking the Cul4b gene were infertile, suggesting that CUL4B plays an important role in regulating female germ cells and/or early embryo development. To this end, this project will use three different transgenic mice expressing Cre enzyme at different developmental stages to mate with our pre-established Cul4b flox mice to obtain mice that knock out Cul4b gene at different stages of oocyte development, and analysis the effect of CUL4B deletion at different stages of oocyte development on the fertility, oocyte development and early embryo development and its mechanism. These findings will not only reveal new functions of the Cul4b gene, but also broaden the understanding of the mechanism of oocyte dysplasia.