Title

Defining the pathways of urogenital schistosomiasis-associated urothelial carcinogenesis through transgenic and bladder wall egg injection models

Document Type

Journal Article

Publication Date

1-1-2018

Journal

Methods in Molecular Biology

Volume

1655

DOI

10.1007/978-1-4939-7234-0_6

Keywords

Bladder cancer; Bladder wall injection; CRE recombinase; Genetic manipulation; p53; Urogenital schistosomiasis

Abstract

© Springer Science+Business Media LLC 2018. 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.

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