细胞周期调节蛋白cyclinA1在多器官中的表达和相关功能的研究
发布时间：2019-05-05 10:58
【摘要】：细胞周期调节与细胞癌变的关系是近年来生命科学研究中的热门课题之一。细胞周期是细胞生命活动的重要过程。正常情况下,细胞在周期时相的变迁中进入增殖、分化、衰老和死亡等生理状态。如果细胞周期调控异常,细胞将进入病理状态,如细胞转化、癌变。二十年前人们在海胆卵中发现一种蛋白,在卵子受精后的每次细胞分裂前开始合成,在细胞分裂结束时迅速消失,并将这种蛋白称作细胞周期调节蛋白。细胞周期调节蛋白的A族成员有胚胎型和体细胞型两种形态。有的生物譬如果蝇只有单一的必需cyclin A基因。其它生物像爪蛙,鼠和人类有两种A型cyclin,一种胚胎特异型的cyclin A1和一种体细胞型的Cyclin A2。 通常认为cyclin A1只表达于减数分裂和非常早期的胚胎,而Cyclin A2在体细胞中都可以见到。在小鼠模型中,唯一必须有cyclin A1参与作用的是精子发生。相反,Cyclin A2是不可缺少的,缺失该基因引起早期胚胎死亡。 后来的研究发现急性粒细胞性白血病、睾丸癌中都有cyclinA1的高表达。这提示我们除了已经报道的正常器官组织外,cyclinA1还参与某些病理性改变。其功能可能还不只是局限于已经报道的内容。 那么cyclinA1表达缺失时,为什么不能产生正常的精子呢?是什么原因使得这些生殖细胞走向凋亡呢?是否象大家通常认为的那样,cyclinA1只表达于野生型小鼠的雄性生殖细胞中,只为精子的发育而存在呢?带着这些问题,我们对特定基因变异的小鼠进行研究。以p53基因敲除的小鼠和cyclinA1基因敲除的小鼠杂交,获取同胎生单基因变异和双基因同时变异的雄性后代共4组12只。比较它们的性腺和生殖细胞发育,并用TUNEL染色法观察和比较生殖细胞的凋亡情况。为了发现基因变异小鼠较为隐蔽或迟发的表现型,我们持续饲养并观察cyclinA1基因变异小鼠和野生型小鼠9个月以上。按照基因型的不同分为两组,其中野生型组25
[Abstract]:The relationship between cell cycle regulation and cell carcinogenesis is one of the hot topics in life science research in recent years. Cell cycle is an important process of cell life activity. Under normal conditions, cells enter the physiological state of proliferation, differentiation, senescence and death during the change of cycle phase. If the cell cycle regulation is abnormal, the cell will enter the pathological state, such as cell transformation, canceration. Twenty years ago, a protein was found in the eggs of sea urchin, which began to synthesize before each cell division after fertilization, disappeared rapidly at the end of cell division, and referred to it as a cell cycle regulatory protein. There are two types of cell cycle regulatory proteins: embryonic type and somatic type. Some organisms, such as fruit flies, have only a single essential cyclin A gene. Other organisms, like frog claw, mouse and human, have two types of A-type cyclin, an embryo-specific cyclin A1 and a somatic Cyclin A2. It is generally believed that cyclin A1 is expressed only in meiosis and very early embryos, while Cyclin A2 can be seen in somatic cells. In mouse models, spermatogenesis is the only one that must be involved in cyclin A1. On the contrary, Cyclin A2 is indispensable, and the deletion of the gene causes early embryo death. Subsequent studies have found high expression of cyclinA1 in acute myeloid leukemia and testicular cancer. This suggests that in addition to the reported normal organ tissues, cyclinA1 is involved in some pathological changes. Its functionality may not be limited to what has been reported. So why can't normal spermatozoa be produced when the expression of cyclinA1 is missing? What causes these germ cells to apoptosis? Is cyclinA1 expressed only in the male germ cells of wild-type mice, as is commonly thought, and only for the development of spermatozoa? With these questions in mind, we studied mice with specific genetic variations. P53 knockout mice and cyclinA1 knockout mice were hybridized to obtain 12 male offspring with single gene mutation and double gene mutation at the same time. Their gonad and germ cell development were compared, and the apoptosis of germ cells was observed and compared by TUNEL staining. In order to find the occult or delayed phenotype of the mutant mice, we kept and observed the cyclinA1 gene mutation mice and wild type mice for more than 9 months. They were divided into two groups according to genotype, of which wild type group 25
【学位授予单位】：中国医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363
本文编号：2469506
[Abstract]:The relationship between cell cycle regulation and cell carcinogenesis is one of the hot topics in life science research in recent years. Cell cycle is an important process of cell life activity. Under normal conditions, cells enter the physiological state of proliferation, differentiation, senescence and death during the change of cycle phase. If the cell cycle regulation is abnormal, the cell will enter the pathological state, such as cell transformation, canceration. Twenty years ago, a protein was found in the eggs of sea urchin, which began to synthesize before each cell division after fertilization, disappeared rapidly at the end of cell division, and referred to it as a cell cycle regulatory protein. There are two types of cell cycle regulatory proteins: embryonic type and somatic type. Some organisms, such as fruit flies, have only a single essential cyclin A gene. Other organisms, like frog claw, mouse and human, have two types of A-type cyclin, an embryo-specific cyclin A1 and a somatic Cyclin A2. It is generally believed that cyclin A1 is expressed only in meiosis and very early embryos, while Cyclin A2 can be seen in somatic cells. In mouse models, spermatogenesis is the only one that must be involved in cyclin A1. On the contrary, Cyclin A2 is indispensable, and the deletion of the gene causes early embryo death. Subsequent studies have found high expression of cyclinA1 in acute myeloid leukemia and testicular cancer. This suggests that in addition to the reported normal organ tissues, cyclinA1 is involved in some pathological changes. Its functionality may not be limited to what has been reported. So why can't normal spermatozoa be produced when the expression of cyclinA1 is missing? What causes these germ cells to apoptosis? Is cyclinA1 expressed only in the male germ cells of wild-type mice, as is commonly thought, and only for the development of spermatozoa? With these questions in mind, we studied mice with specific genetic variations. P53 knockout mice and cyclinA1 knockout mice were hybridized to obtain 12 male offspring with single gene mutation and double gene mutation at the same time. Their gonad and germ cell development were compared, and the apoptosis of germ cells was observed and compared by TUNEL staining. In order to find the occult or delayed phenotype of the mutant mice, we kept and observed the cyclinA1 gene mutation mice and wild type mice for more than 9 months. They were divided into two groups according to genotype, of which wild type group 25
【学位授予单位】：中国医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363
【引证文献】
相关硕士学位论文 前2条
1 刘志文;SPATA12基因作为肿瘤抑制因子的实验研究[D];湖南大学;2011年
2 徐博慧;藻红蛋白诱导人乳腺癌细胞MCF-7凋亡的细胞周期途径研究[D];哈尔滨商业大学;2010年
，本文编号：2469506
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