Defining the Pathways of Urogenital Schistosomiasis-Associated Urothelial Carcinogenesis through Transgenic and Bladder Wall Egg Injection Models
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.
Key wordsBladder cancer Urogenital schistosomiasis Bladder wall injection Genetic manipulation CRE recombinase p53
This work was supported by NIH R56AI119168. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the funders. The funders had no role in the preparation of the manuscript and the decision to publish. We appreciate the significant contributions by the previous Hsieh laboratory members and collaborators in the described projects, including but not limited to Chi-Ling Fu, Jared Honeycutt, Justin Odegaard, Olfat Hamman, and De’Broski R. Herbert.
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