【摘要】：細(xì)胞周期調(diào)節(jié)與細(xì)胞癌變的關(guān)系是近年來(lái)生命科學(xué)研究中的熱門(mén)課題之一。細(xì)胞周期是細(xì)胞生命活動(dòng)的重要過(guò)程。正常情況下,細(xì)胞在周期時(shí)相的變遷中進(jìn)入增殖、分化、衰老和死亡等生理狀態(tài)。如果細(xì)胞周期調(diào)控異常,細(xì)胞將進(jìn)入病理狀態(tài),如細(xì)胞轉(zhuǎn)化、癌變。二十年前人們?cè)诤Ｄ懧阎邪l(fā)現(xiàn)一種蛋白,在卵子受精后的每次細(xì)胞分裂前開(kāi)始合成,在細(xì)胞分裂結(jié)束時(shí)迅速消失,并將這種蛋白稱作細(xì)胞周期調(diào)節(jié)蛋白。細(xì)胞周期調(diào)節(jié)蛋白的A族成員有胚胎型和體細(xì)胞型兩種形態(tài)。有的生物譬如果蠅只有單一的必需cyclin A基因。其它生物像爪蛙,鼠和人類有兩種A型cyclin,一種胚胎特異型的cyclin A1和一種體細(xì)胞型的Cyclin A2。 通常認(rèn)為cyclin A1只表達(dá)于減數(shù)分裂和非常早期的胚胎,而Cyclin A2在體細(xì)胞中都可以見(jiàn)到。在小鼠模型中,唯一必須有cyclin A1參與作用的是精子發(fā)生。相反,Cyclin A2是不可缺少的,缺失該基因引起早期胚胎死亡。 后來(lái)的研究發(fā)現(xiàn)急性粒細(xì)胞性白血病、睪丸癌中都有cyclinA1的高表達(dá)。這提示我們除了已經(jīng)報(bào)道的正常器官組織外,cyclinA1還參與某些病理性改變。其功能可能還不只是局限于已經(jīng)報(bào)道的內(nèi)容。 那么cyclinA1表達(dá)缺失時(shí),為什么不能產(chǎn)生正常的精子呢?是什么原因使得這些生殖細(xì)胞走向凋亡呢?是否象大家通常認(rèn)為的那樣,cyclinA1只表達(dá)于野生型小鼠的雄性生殖細(xì)胞中,只為精子的發(fā)育而存在呢?帶著這些問(wèn)題,我們對(duì)特定基因變異的小鼠進(jìn)行研究。以p53基因敲除的小鼠和cyclinA1基因敲除的小鼠雜交,獲取同胎生單基因變異和雙基因同時(shí)變異的雄性后代共4組12只。比較它們的性腺和生殖細(xì)胞發(fā)育,并用TUNEL染色法觀察和比較生殖細(xì)胞的凋亡情況。為了發(fā)現(xiàn)基因變異小鼠較為隱蔽或遲發(fā)的表現(xiàn)型,我們持續(xù)飼養(yǎng)并觀察cyclinA1基因變異小鼠和野生型小鼠9個(gè)月以上。按照基因型的不同分為兩組,其中野生型組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
【學(xué)位授予單位】：中國(guó)醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R363

【引證文獻(xiàn)】

相關(guān)碩士學(xué)位論文 前2條

1 劉志文;SPATA12基因作為腫瘤抑制因子的實(shí)驗(yàn)研究[D];湖南大學(xué);2011年

2 徐博慧;藻紅蛋白誘導(dǎo)人乳腺癌細(xì)胞MCF-7凋亡的細(xì)胞周期途徑研究[D];哈爾濱商業(yè)大學(xué);2010年

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本文編號(hào)：2469506