Mbanefo Evaristus C, Hsieh Michael H
Children's National Medical Center, 111 Michigan Ave. NW, Washington, DC, 20010, USA.
Biomedical Research Institute, 9410 Key West Ave., Rockville, MD, 20850, USA.
Methods Mol Biol. 2018;1655:67-76. doi: 10.1007/978-1-4939-7234-0_6.
Urogenital schistosomiasis (infection with Schistosoma 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.
泌尿生殖系统血吸虫病（感染埃及血吸虫）是膀胱癌发生的主要原因。然而，导致膀胱癌发生的后遗症的确切机制尚不清楚，主要是因为缺乏易于处理的小鼠模型。我们通过将寄生虫卵壁内注射到膀胱壁来模拟寄生虫卵在膀胱中的滞留，从而建立了泌尿生殖系统血吸虫病的小鼠模型。这种方法概括了在受感染人类中观察到的许多后遗症。在这里，我们描述了将这种手术技术与成熟的转基因小鼠品系相结合的程序，以剖析癌症相关基因在膀胱癌发生起始和发展中的作用。所描述的方法利用CRE介导的flox活性，在用膀胱壁注射虫卵对小鼠进行攻击之前，使小鼠p53单倍体不足。这些技术可能适用于研究其他促癌和抑癌基因在泌尿生殖系统血吸虫病相关尿路上皮癌发生中的作用。
