Defining the Pathways of Urogenital Schistosomiasis-Associated Urothelial Carcinogenesis through Transgenic and Bladder Wall Egg Injection Models.
Defining the Pathways of Urogenital Schistosomiasis-Associated Urothelial Carcinogenesis through Transgenic and Bladder Wall Egg Injection Models.
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DOI：
10.1007/978-1-4939-7234-0_6
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发表时间：
2018
影响因子：
--
通讯作者：
E. Mbanefo;M. Hsieh
中科院分区：
文献类型：
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作者：
E. Mbanefo;M. Hsieh
泌尿生殖道血吸虫病（埃及血吸虫感染）是膀胱癌发生的主要原因。然而，导致膀胱癌发展的后遗症的确切机制知之甚少，主要是因为缺乏易处理的小鼠模型。我们通过膀胱壁内注射寄生虫卵来模拟寄生虫卵在膀胱中的捕获，建立了泌尿生殖道血吸虫病小鼠模型。这种方法概括了在感染者中观察到的许多后遗症。在这里，我们描述了利用这种手术技术结合成熟的转基因小鼠品系的程序，以解剖癌症相关基因在膀胱癌发生的启动和建立中的作用。所描述的方法利用CRE介导的flox活性，使小鼠p53单倍不足，然后用膀胱壁卵注射攻击它们。这些技术有可能适用于研究其他促癌基因和抑癌基因在泌尿生殖道染色体异常相关尿路上皮癌发生中的作用。
Urogenital schistosomiasis (infection withSchistosoma haematobium) is a major cause of bladder carcinogenesis. However, the exact mechanisms of the sequelae leading up to the development of bladder cancer are poorly understood, mainly because of a dearth of tractable mouse models. We developed a mouse model of urogenital schistosomiasis through intramural injection of parasite eggs into the bladder wall to mimic the trapping of parasite eggs in the bladder. This approach recapitulates many of the sequelae observed in infected humans. Here, we describe procedures for utilizing this surgical technique in combination with well-established transgenic mouse strains to dissect the role of cancer-related genes in the initiation and establishment of bladder carcinogenesis. The described method utilizes CRE-mediated flox activity to render mice p53 haploinsufficient before challenging them with bladder wall egg injection. These techniques are potentially amenable to studying the role of other pro-carcinogenic and cancer suppressor gene(s) in urogenital schistosomiasis-associated urothelial carcinogenesis.