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Am J Physiol Renal Physiol 289: F562-F568, 2005. First published April 19, 2005; doi:10.1152/ajprenal.00368.2004
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Gene deletion in urothelium by specific expression of Cre recombinase

Lan Mo,1 Jin Cheng,1 Eva Y.-H. P. Lee,2 Tung-Tien Sun,1,3,4 and Xue-Ru Wu1,5,6

Departments of 1Urology, 5Microbiology, 3Dermatology, and 4Pharmacology, New York University Cancer Institute, New York University School of Medicine, New York; 6Veterans Affairs Medical Center in Manhattan, New York, New York; and 2Departments of Developmental and Cell Biology and Biological Chemistry, University of California, Irvine, California

Submitted 29 September 2004 ; accepted in final form 13 April 2005

Urothelium that lines almost the entire urinary tract acts as a permeability barrier and is involved in the pathogenesis of major urinary diseases, including urothelial carcinoma, urinary tract infection, and interstitial cystitis. However, investigation of urothelial biology and diseases has been hampered by the lack of tissue-specific approaches. To address this deficiency, we sought to develop a urothelium-specific knockout system using the Cre/loxP strategy. Transgenic mouse lines were generated in which a 3.6-kb mouse uroplakin II (UPII) promoter was used to drive the expression of Cre recombinase (Cre). Among the multiple tissues analyzed, Cre was found to be expressed exclusively in the urothelia of the transgenic mice. Crossing a UPII-Cre transgenic line with a ROSA26-LacZ reporter line, in which LacZ expression depends on Cre-mediated deletion of a floxed "stop" sequence, led to LacZ expression only in the urothelium. Gene recombination was also observed when the UPII-Cre line was crossed to an independent line in which a part of the p53 gene was flanked by the loxP sequences (floxed p53). Truncation of the p53 gene and mRNA was observed exclusively in the urothelia of double transgenic mice harboring both the UPII-Cre transgene and the floxed p53 allele. These results demonstrate for the first time the feasibility and potentially wide applicability of the UPII-Cre transgenic mice to inactivate any genes of interest in the urothelium.

urothelium; bladder; tissue-specific gene knockout; Cre recombinase; uroplakin; transgenic mice



Address for reprint requests and other correspondence: X.-R. Wu, Dept. of Urology, New York Univ. School of Medicine, VA Medical Center in Manhattan, 423 East 23 St., Rm. 18064 South, New York, New York 10010 (e-mail: xue-ru.wu{at}med.nyu.edu)




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