近日，PLoS ONE在线发表了营养所王福俤研究组的研究论文“Slc39a7/zip7 plays a critical role in development and zinc homeostasis in zebrafish”。该研究结果揭示锌转运蛋白Zip7在斑马鱼胚胎发育及维持锌离子稳态过程中发挥重要作用。
必需微量元素锌是机体多种酶的必需组分或激活因子, 参与DNA复制、蛋白合成、细胞分化等，与发育、脑功能、骨骼生长、免疫功能及生殖健康等密切相关，研究已发现锌稳态受SLC39A/Zip和SLC30A/ZnT两个锌转运家族调控。王福俤研究员在国外工作期间详细研究了SLC39A/Zip家族中ZIP1、ZIP2、ZIP3、ZIP4、ZIP5转运锌离子的功能及机制，并阐明了ZIP4突变导致小肠摄取锌离子障碍而引发人类遗传性疾病肠病性肢端皮炎的分子机理（Human Molecular Genentics,2004）。Zip7是SLC39A/Zip家族成员，有研究发现Zip7主要分布在细胞高尔基体和内质网，对维持细胞生长与凋亡具有作用。然而之前有关Zip7的研究主要是在细胞水平进行的，Zip7对整个机体功能及发育的作用尚不清楚。
颜广、张玉超和俞俊磊等研究生在王福俤研究员的指导下利用morpholino-oligonucleotides (MO)技术成功构建了Zip7 knockdown斑马鱼模型。研究发现Zip7基因沉默以后胚胎发育异常，采用X射线荧光光谱技术（XRF）从整体水平观察了锌在机体中的分布规律，发现Zip7通过调控锌在机体不同组织和器官中的分布来影响机体发育，其作用部位主要是头部与眼睛。
此外，在进行此项研究过程中，王福俤研究组与健康所科研人员合作，建立了微量元素代谢新基因的ENU化学诱变正向遗传学筛选平台，建成一次高通量（约3000个基因组）的斑马鱼金属离子代谢异常突变体筛选，已筛选出20余个对高浓度致死剂量锌离子、铜离子或镉离子呈抵抗或敏感的斑马鱼突变株，为进一步研究发现调控微量元素的新基因，理解金属代谢稳态的分子机制、明确微量元素稳态代谢紊乱相关疾病奠定了基础。
本项目得到国家科技部、国家自然科学基金委、中国科学院及上海市科委等经费资助。（生物谷Bioon.com）
doi:10.1371/journal.pone.0042939
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Slc39a7/zip7 Plays a Critical Role in Development and Zinc Homeostasis in Zebrafish
Guang Yan, Yuchao Zhang, Junlei Yu, Yu Yu, Fan Zhang, Zhuzhen Zhang, Aimin Wu, Xianghua Yan, Yi Zhou, Fudi Wang
Background
Slc39a7/Zip7, also known as Ke4, is a member of solute carrier family 39 (Slc39a) and plays a critical role in regulating cell growth and death. Because the function of Zip7 in vivo was unclear, the present study investigated the function of zip7 in vertebrate development and zinc metabolism using zebrafish as a model organism.
Principal Finding
Using real-time PCR to determine the gene expression pattern of zip7 during zebrafish development, we found that zip7 mRNA is expressed throughout embryonic development and into maturity. Interestingly, whole mount in situ hybridization revealed that while zip7 mRNA is ubiquitously expressed until 12 hours post-fertilization (hpf); at 24 hpf and beyond, zip7 mRNA was specifically detected only in eyes. Morpholino-antisense (MO) gene knockdown assay revealed that downregulation of zip7 expression resulted in several morphological defects in zebrafish including decreased head size, smaller eyes, shorter palates, and shorter and curved spinal cords. Analysis by synchrotron radiation X-ray fluorescence (SR-XRF) showed reduced concentrations of zinc in brain, eyes, and gills of zip7-MO-injected embryos. Furthermore, incubation of the zip7 knockdown embryos in a zinc-supplemented solution was able to rescue the MO-induced morphological defects.
Significance
Our data suggest that zip7 is required for eye, brain, and skeleton formation during early embryonic development in zebrafish. Moreover, zinc supplementation can partially rescue defects resulting from zip7 gene knockdown. Taken together, our data provide critical insight into a novel function of zip7 in development and zinc homeostasis in vivo in zebrafish.
