近日，PLoS ONE在線發(fā)表了營(yíng)養(yǎng)所王福俤研究組的研究論文“Slc39a7/zip7 plays a critical role in development and zinc homeostasis in zebrafish”,。該研究結(jié)果揭示鋅轉(zhuǎn)運(yùn)蛋白Zip7在斑馬魚胚胎發(fā)育及維持鋅離子穩(wěn)態(tài)過(guò)程中發(fā)揮重要作用。
必需微量元素鋅是機(jī)體多種酶的必需組分或激活因子, 參與DNA復(fù)制,、蛋白合成、細(xì)胞分化等,，與發(fā)育,、腦功能、骨骼生長(zhǎng),、免疫功能及生殖健康等密切相關(guān),，研究已發(fā)現(xiàn)鋅穩(wěn)態(tài)受SLC39A/Zip和SLC30A/ZnT兩個(gè)鋅轉(zhuǎn)運(yùn)家族調(diào)控。王福俤研究員在國(guó)外工作期間詳細(xì)研究了SLC39A/Zip家族中ZIP1,、ZIP2,、ZIP3、ZIP4,、ZIP5轉(zhuǎn)運(yùn)鋅離子的功能及機(jī)制,，并闡明了ZIP4突變導(dǎo)致小腸攝取鋅離子障礙而引發(fā)人類遺傳性疾病腸病性肢端皮炎的分子機(jī)理（Human Molecular Genentics,2004）,。Zip7是SLC39A/Zip家族成員，有研究發(fā)現(xiàn)Zip7主要分布在細(xì)胞高爾基體和內(nèi)質(zhì)網(wǎng),，對(duì)維持細(xì)胞生長(zhǎng)與凋亡具有作用,。然而之前有關(guān)Zip7的研究主要是在細(xì)胞水平進(jìn)行的，Zip7對(duì)整個(gè)機(jī)體功能及發(fā)育的作用尚不清楚,。
顏廣,、張玉超和俞俊磊等研究生在王福俤研究員的指導(dǎo)下利用morpholino-oligonucleotides (MO)技術(shù)成功構(gòu)建了Zip7 knockdown斑馬魚模型。研究發(fā)現(xiàn)Zip7基因沉默以后胚胎發(fā)育異常,，采用X射線熒光光譜技術(shù)（XRF）從整體水平觀察了鋅在機(jī)體中的分布規(guī)律,，發(fā)現(xiàn)Zip7通過(guò)調(diào)控鋅在機(jī)體不同組織和器官中的分布來(lái)影響機(jī)體發(fā)育，其作用部位主要是頭部與眼睛,。
此外,，在進(jìn)行此項(xiàng)研究過(guò)程中，王福俤研究組與健康所科研人員合作,，建立了微量元素代謝新基因的ENU化學(xué)誘變正向遺傳學(xué)篩選平臺(tái),，建成一次高通量（約3000個(gè)基因組）的斑馬魚金屬離子代謝異常突變體篩選，已篩選出20余個(gè)對(duì)高濃度致死劑量鋅離子,、銅離子或鎘離子呈抵抗或敏感的斑馬魚突變株,，為進(jìn)一步研究發(fā)現(xiàn)調(diào)控微量元素的新基因，理解金屬代謝穩(wěn)態(tài)的分子機(jī)制,、明確微量元素穩(wěn)態(tài)代謝紊亂相關(guān)疾病奠定了基礎(chǔ),。
本項(xiàng)目得到國(guó)家科技部、國(guó)家自然科學(xué)基金委,、中國(guó)科學(xué)院及上海市科委等經(jīng)費(fèi)資助。（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.
