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南京医科大学学报(自然科学版)                                  第44卷第4期
               ·462 ·                     Journal of Nanjing Medical University(Natural Sciences)   2024年4月


             ·基础研究·

              Coq4基因全敲除小鼠胚胎发育的表型分析



              贺雪珂 ,姜志胜 ,杨中州 ,姜 淼             1*
                                     2
                             1
                     1
               南华大学心血管疾病研究所,动脉硬化学湖南省重点实验室,湖南省动脉硬化性疾病国际科技创新合作基地,湖南                                          衡阳
              1
              421000;南京大学医学院基础医学系,江苏             南京   210008
                     2

             [摘    要] 目的:通过分析辅酶 Q 生物合成蛋白 4 同系物(coenzyme Q biosynthesis protein 4 homolog ,COQ4)的编码基因Coq4
              敲除(Coq4 )小鼠表型,探讨Coq4在小鼠胚胎发育中的作用。方法:引进Coq4基因全身杂合(Coq4 )小鼠模型,利用基因组
                       -/-
                                                                                           +/-
              PCR鉴定小鼠基因型。观察并记录Coq4 小鼠后代出生情况;通过解剖、组织学和免疫荧光法,观察野生型(wild type,WT)和
                                             +/-
              Coq4 胚胎和胎盘组织的形态结构。结果: Coq4 小鼠在胚胎日(embryonic day,E)7.5 d(E7.5)出现原肠胚形成障碍,于E10.5死
                                                   -/-
                  -/-
                                              -/-
              亡。组织形态分析显示,与WT相比, Coq4 小鼠胚胎发育严重迟缓,胎盘结构缺陷。免疫荧光染色分析发现,Coq4 小鼠胎盘滋
                                                                                                    -/-
              养层细胞侵袭能力减弱。结论: Coq4基因敲除导致小鼠发生胎盘缺陷和原肠胚形成障碍, Coq4为小鼠胚胎发育所必需的基因。
             [关键词] 滋养层细胞;胎盘;胚外外胚层;原肠胚
             [中图分类号] R394.1                   [文献标志码] A                       [文章编号] 1007⁃4368(2024)04⁃462⁃07
              doi:10.7655/NYDXBNSN231030

              Phenotypic analysis of embryonic development in mice with global knockout of the Coq4
              gene

                       1
                                      1
                                                       2
              HE Xueke ,JIANG Zhisheng ,YANG Zhongzhou ,JIANG Miao 1*
              1 Institute of Cardiovascular Disease,Key Laboratory for Arteriosclerology of Hunan Province,International Joint
                                                                                    2
              Laboratory for Arteriosclerotic Disease,University of South China,Hengyang 421000;Department of Basic Medicine,
              School of Medicine,Nanjing University,Nanjing 210008,China

             [Abstract] Objective:To elucidate the physiological functions of coenzyme Q biosynthesis protein 4 homolog(COQ4)in mammals
                                      -/-
              by using Coq4 knockout(Coq4 )mice. Methods: Coq4 global heterozygous mouse models were introduced,and the different
              genotypes of mice were detected by genomic PCR. The phenotypes,growth,reproduction of Coq4  +/-  mice were observed and recorded.
              The morphology and structure of embryonic and placental tissues of wild type(WT)and Coq4 -/-  mice were studied by anatomic and
              histological analyses as well as immunofluorescence assay. Results: Coq4  -/-  mice exhibited an impaired gastrulation on embryonic day

             (E)7.5(E7.5)and were died on E10.5. Morphological analysis showed severely retarded embryonic development with obvious defective
                                   -/-
              placental structures in Coq4 mice,compared with the WT mice. Immunofluorescence analysis revealed that trophoblast cell invasion
              was diminished in the placenta of Goq4 -/-  mice. Conclusion:Knockout of Coq4 gene leads to impaired placenta and gastrula formation
              in mice. Coq4 is essential for embryonic development.
             [Key word] trophoblast cell;placenta;extra⁃embryonic ectoderm;gastrulation
                                                                            [J Nanjing Med Univ,2024,44(04):462⁃468]





                  辅酶Q(coenzyme Q,CoQ)是一种由苯醌环和类                  异戊二烯链组成的脂质分子,广泛分布于所有真核
                                                                细胞的细胞膜中。异戊二烯的长度可因物种不同而
             [基金项目] 国家重点研发计划专项(2019YFA0801601,
                                                                改变,6个异戊二烯形成酵母的辅酶Q6(CoQ6),8个
              2018YFA0801100);国家自然科学基金(32101018);湖南省自
              然科学基金(2023JJ30522)                                异戊二烯形成大肠杆菌中的辅酶 Q8(CoQ8),10 个
                                                                                          [1-2]
              ∗                                                                              。CoQ10 可以接受
              通信作者(Corresponding author),E⁃mail:miao_jiang@usc.edu.cn  异戊二烯形成人类的 CoQ10
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