斑马鱼bok基因在性腺发育中的功能研究
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摘要
斑马鱼的繁殖力强、胚胎透明,是发育生物学、分子生物学和遗传学方面研究中重要的模式生物。Bcl-2(B cell lymphoma/lewkmia-2)家族是决定真核细胞存活或凋亡的关键调控因子。bok (Bcl-2-related ovarian killer)是Bcl-2家族成员中的促凋亡成员,斑马鱼中含有bokl和bok2两种亚型。本研究通过使斑马鱼bok基因在性腺中特异表达,以确定bok在性腺发育中的功能。
本研究以斑马鱼为实验材料,首先采用RT-PCR技术和荧光定量PCR技术检测bokl和bok2在斑马鱼不同组织器官、胚胎发育时期的表达模式。结果表明bokl除不能在斑马鱼的肝中表达在其他组织中均能检测到,如在眼、卵巢、精巢、脑、肠中表达量较高,在心、肾、脾也有表达；bok2在斑马鱼的卵巢、精巢、眼睛、肝中表达,且在眼睛和卵巢中表达量最高,而在其它的组织器官如脑、肠、心、脾、肾中均未检测到其表达。检测胚胎早期发育的不同时期,发现bokl在发育早期持续低水平低的表达；bok2从受精后即有较高水平的表达,一直持续到30%外包期,之后表达量降低,从90%外胞期表达量开始升高。荧光定量PCR检测。结果显示,未受精胚胎中bok2远高于bokl的表达。说明bok1、bok2都为母源性基因,除了在性腺中表达外还在其它组织中表达,推测这两个基因功能,除了影响性腺发育和配子发生,也对其它组织器官发育有作用。
构建beta-actin-bokl-GFP-nanos和beta-actin-bok2-GFP-nanos重组质粒与tol2转座酶mRNA共同注射斑马鱼1细胞期受精卵,荧光显微镜观察发现得到除性腺特外其它组织也有绿色荧光的转基因鱼。得到P0代阳性转基因鱼,与野生鱼交配后得到转beta-actin-bok2-GFP-nanos的F1代饲养至性成熟,解剖F1代发现卵巢中较小的细胞有绿色荧光,而成熟的细胞没有荧光,并对卵巢进行冰冻切片观察,认为转基因鱼与野生鱼在在形态学上几乎没有差异。我们最后得到可育的转基因鱼,认为bok2的过表达对抑制性腺发育的作用不大。还需要进一步染色或凋亡分析来确定过表达bok的转基因鱼的性腺是否发生异常凋亡,或者利用特异性的启动子使bok特异在性腺中表达,进而深入确定bok的功能。
Zebrafish which has strong fertility, the embryo transparent and development speed, is an important model of molecular biology, developmental biology and genetics study. Members of the Bcl-2family are critical mediators of the delicate balance between survival and apoptosis in eucaryotic cells. Bcl-2family is a kind of very conservative protein, can be divided into three categories:anti-apoptotic Bcl-2family, pro-apoptosis Bax subfamily, and BH3-only the family. Bok (Bcl-2-related ovarian killer) is considered a pro-apoptotic member of the Bcl-2family, zebrafish contains bokl and bok2two subtype. In this study, we over-expression Bok in zebrafish, to understand the function of bok in the gonadal development, if we could get gonadal infertility of genetically modified fish,we can controlling genetically modified (GM) fish breeding and meet the standards of biological and environment safety for other GM species.
The experimental materials is zebrafish, firstly,we use the RT-PCR technology and fluorescence quantitative PCR technology detection bokl and bok2expression in zebrafish different organs and embryonic development period of representation. The results show that bokl in zebrafish eyes, brain, intestine, ovarian, testis could detect the bokl mRNA high expressions; heart, kidney, and spleen also has weak expressed and no expression in liver; bok2expressions in zebrafish ovarian, testis, eyes, liver can be detected, and expression in the highest amount, and in other organs such as the brain, heart, spleen and kidney were not detected its expression. detection different early embryo developmental period, show that bokl in512cells begin to express, until90%epiboly it began to appear to high expression;after fertilization bok2has a high level of expression, after30%epiboly bok2expression reduction, until to90%epiboly the expression began to rise. Fluorescence quantitative PCR detection showed that in unfertilized embryo, bok2expression is much higher than bokl. Together, the bokl and bok2are maternal gene. bok mRNA expression is most abundant in the testis and ovaries, bok was, however, also readily detected in many additional organs. This indicates that bok may have a wider role rather than being limited to the godan developmet and form gamete.
Then build beta-actin-bokl-GFP-nanos and beta-actin-bok2-GFP-nanos restructuring plasmid and with tol2mRNA co-injection zebrafish1-cell fertilized egg, fluorescence microscope observed that all the organs can detect green fluorescent, beta-actin promoter drive random integration. Get P0transgenic fish, mating with WT, feeding F1offspring to sexual maturity. Dissection the F1ovary, find that there is green fluorescence in the smaller cells, while not in the mature cells. Ovarian frozen sections observed that there was no morphology difference between the transgenic fish and wild fish. We need further study by staining, apoptosis analysis or using of specific gonad promoters to determine the function of the bok.
本研究以斑马鱼为实验材料,首先采用RT-PCR技术和荧光定量PCR技术检测bokl和bok2在斑马鱼不同组织器官、胚胎发育时期的表达模式。结果表明bokl除不能在斑马鱼的肝中表达在其他组织中均能检测到,如在眼、卵巢、精巢、脑、肠中表达量较高,在心、肾、脾也有表达；bok2在斑马鱼的卵巢、精巢、眼睛、肝中表达,且在眼睛和卵巢中表达量最高,而在其它的组织器官如脑、肠、心、脾、肾中均未检测到其表达。检测胚胎早期发育的不同时期,发现bokl在发育早期持续低水平低的表达；bok2从受精后即有较高水平的表达,一直持续到30%外包期,之后表达量降低,从90%外胞期表达量开始升高。荧光定量PCR检测。结果显示,未受精胚胎中bok2远高于bokl的表达。说明bok1、bok2都为母源性基因,除了在性腺中表达外还在其它组织中表达,推测这两个基因功能,除了影响性腺发育和配子发生,也对其它组织器官发育有作用。
构建beta-actin-bokl-GFP-nanos和beta-actin-bok2-GFP-nanos重组质粒与tol2转座酶mRNA共同注射斑马鱼1细胞期受精卵,荧光显微镜观察发现得到除性腺特外其它组织也有绿色荧光的转基因鱼。得到P0代阳性转基因鱼,与野生鱼交配后得到转beta-actin-bok2-GFP-nanos的F1代饲养至性成熟,解剖F1代发现卵巢中较小的细胞有绿色荧光,而成熟的细胞没有荧光,并对卵巢进行冰冻切片观察,认为转基因鱼与野生鱼在在形态学上几乎没有差异。我们最后得到可育的转基因鱼,认为bok2的过表达对抑制性腺发育的作用不大。还需要进一步染色或凋亡分析来确定过表达bok的转基因鱼的性腺是否发生异常凋亡,或者利用特异性的启动子使bok特异在性腺中表达,进而深入确定bok的功能。
Zebrafish which has strong fertility, the embryo transparent and development speed, is an important model of molecular biology, developmental biology and genetics study. Members of the Bcl-2family are critical mediators of the delicate balance between survival and apoptosis in eucaryotic cells. Bcl-2family is a kind of very conservative protein, can be divided into three categories:anti-apoptotic Bcl-2family, pro-apoptosis Bax subfamily, and BH3-only the family. Bok (Bcl-2-related ovarian killer) is considered a pro-apoptotic member of the Bcl-2family, zebrafish contains bokl and bok2two subtype. In this study, we over-expression Bok in zebrafish, to understand the function of bok in the gonadal development, if we could get gonadal infertility of genetically modified fish,we can controlling genetically modified (GM) fish breeding and meet the standards of biological and environment safety for other GM species.
The experimental materials is zebrafish, firstly,we use the RT-PCR technology and fluorescence quantitative PCR technology detection bokl and bok2expression in zebrafish different organs and embryonic development period of representation. The results show that bokl in zebrafish eyes, brain, intestine, ovarian, testis could detect the bokl mRNA high expressions; heart, kidney, and spleen also has weak expressed and no expression in liver; bok2expressions in zebrafish ovarian, testis, eyes, liver can be detected, and expression in the highest amount, and in other organs such as the brain, heart, spleen and kidney were not detected its expression. detection different early embryo developmental period, show that bokl in512cells begin to express, until90%epiboly it began to appear to high expression;after fertilization bok2has a high level of expression, after30%epiboly bok2expression reduction, until to90%epiboly the expression began to rise. Fluorescence quantitative PCR detection showed that in unfertilized embryo, bok2expression is much higher than bokl. Together, the bokl and bok2are maternal gene. bok mRNA expression is most abundant in the testis and ovaries, bok was, however, also readily detected in many additional organs. This indicates that bok may have a wider role rather than being limited to the godan developmet and form gamete.
Then build beta-actin-bokl-GFP-nanos and beta-actin-bok2-GFP-nanos restructuring plasmid and with tol2mRNA co-injection zebrafish1-cell fertilized egg, fluorescence microscope observed that all the organs can detect green fluorescent, beta-actin promoter drive random integration. Get P0transgenic fish, mating with WT, feeding F1offspring to sexual maturity. Dissection the F1ovary, find that there is green fluorescence in the smaller cells, while not in the mature cells. Ovarian frozen sections observed that there was no morphology difference between the transgenic fish and wild fish. We need further study by staining, apoptosis analysis or using of specific gonad promoters to determine the function of the bok.
引文
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