UT-B基因敲除雌性小鼠生殖延迟原因与机制的研究

发布时间：2018-04-18 11:24

本文选题：尿素通道蛋白B + 基因敲除　；参考：《吉林大学》2006年博士论文

【摘要】：尿素通道蛋白(Urea Transporters,UTs)是介导尿素顺浓度梯度跨生物膜转运的通道蛋白。目前,已克隆出哺乳动物的UTs包括UT-A、UT-B两个家族。UT-B在肾脏、心脏、脑、睾丸等组织器官有表达,尤其在红细胞膜上呈高表达。虽然,对UT-B的基因和蛋白结构的研究已经取得了显著成果。但是,对其生理功能所知有限。因此,为进行功能研究建立了UT-B基因敲除模型。已经发现UT-B基因敲除小鼠,因肾内尿素逆流交换过程被阻断而使尿浓缩能力下降,并发现Jknull表型,即UT-B基因缺失患者的红细胞对2mol/L尿素有溶血抵抗性。由于对UT-B基因敲除小鼠其他各脏器与系统的研究甚少,本论文主要针对雌性生殖系统进行研究:来自美国加州大学UT-B基因敲除种鼠,繁殖后获得雌性小鼠的基因型与生物特性的研究;探讨UT-B基因敲除雌性小鼠生殖延迟原因与机制;UT-B基因敲除雌鼠生殖腺AQP1和AQP8mRNA表达及其意义的研究。得出以下结论:1.成功搭建了一个UT-B基因敲除小鼠的基因型检测技术平台。2.UT-B在雌性生殖器官表达,说明UT-B在雌性生殖系统的尿素转运中起重要作用。3.UT-B基因敲除雌鼠生殖延迟,并且可作为生殖延迟的动物模型。4.4w和6w龄UT-B-/-雌鼠雌激素水平低下,可能是导致UT-B基因敲除雌鼠生殖延迟的直接原因。5.丘脑-垂体-性腺轴异常是生殖延迟的UT-B基因敲除雌鼠雌激素水平低下的原因。6.UT-B基因敲除后水通道蛋白表达增加,可能是一种代偿性的变化。关于UT-B基因与蛋白在雌鼠生殖器官与胎盘的表达,以及UT-B基因敲除雌鼠生殖延迟及其机制的研究发现,在国内外均属首次报道。本研究的结果将为雌性生殖延迟的机制与调节提供实验依据,为进一步探讨UT-B在生殖系统及神经-内分泌系统的研究奠定基础。
[Abstract]:Urea Channel protein (Urea Transporters) is a channel protein that mediates the translocation of urea through biofilm.At present, mammalian UTs including UT-An UT-B family. UT-B is expressed in kidney, heart, brain, testis and other tissues, especially on erythrocyte membrane.Significant results have been achieved in the study of the gene and protein structure of UT-B.However, knowledge of its physiological function is limited.Therefore, the UT-B gene knockout model was established for functional study.UT-B knockout mice have been found to have reduced urinary concentration due to the interdiction of urea countercurrent exchange in the kidney, and Jknull phenotype has been found, that is, the erythrocytes of UT-B gene deficient patients have hemolytic resistance to 2mol/L urea.Due to the lack of studies on other organs and systems in UT-B knockout mice, this paper focuses on the female reproductive system: UT-B gene knockout mice from the University of California, USA.The genotypes and biological characteristics of female mice were obtained after reproduction, and the reasons and mechanism of reproductive delay in female mice with UT-B gene knockout were investigated. The expression and significance of AQP1 and AQP8mRNA in gonad of female mice with UT-B gene knockout were studied.Draw the following conclusion: 1.A platform for genotypic detection of UT-B knockout mice was successfully established. 2. UT-B expression in female reproductive organs, indicating that UT-B plays an important role in urea transport in female reproductive system. 3. UT-B gene knockout female mice are delayed in reproduction.And it can be used as animal model of reproductive delay. 4.4w and 6w old UT-B-r-females have low estrogen level, which may be the direct cause of reproductive delay in UT-B knockout female mice.The abnormal axis of thalamus-pituitary-gonad is the cause of the low estrogen level in the reproductive delayed UT-B knockout female. 6. The increase of aquaporin expression after the knockout of UT-B gene may be a compensatory change.The expression of UT-B gene and protein in female reproductive organs and placenta, and the reproductive delay and its mechanism of UT-B gene knockout in female mice are reported for the first time at home and abroad.The results of this study will provide experimental basis for the mechanism and regulation of female reproductive delay and lay a foundation for the further study of UT-B in the reproductive system and neuroendocrine system.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363

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