Gene expression data from FGFR3 induced mouse bladder tumors

Somatic mutations of the fibroblast growth factor receptor 3 (FGFR3) are one of the most frequent genetic alterations in bladder carcinomas. We report here that human-FGFR3-S249C expression in urothelial cells of transgenic mice induces low-grade papillary tumors presenting genomic instability and resembling human pTa urothelial tumors at the transcriptomic level. Mutated-FGFR3 expression levels impacted the incidence of tumor formation and could account for the tissue specificity of human mutated FGFR3-driven tumors restricted to epithelia presenting high normal expression levels of FGFR3. The expression of a human FGFR3-IIIb carrying the S249C mutation was targeted to the urothelium of mice by using the 5’ regulatory region of the mouse uroplakin II promoter. The UII-FGFR3b-S249C construct was obtained by inserting the 3.6 kb murine uroplakin II promoter (UII) (40) excised with SalI and BamHI into the same restriction sites of the vector containing the β-globin intron 2 and the 3’ polyadenylation sequences of SV40 (41) followed by the insertion of a human S249C mutated FGFR3 cDNA excised with XbaI and HindIII into the SmaI site of this vector. All PCR-generated segments were verified by sequencing both strands. The pUII-hFGFR3b-S249C constructs excised with KpnI were purified and microinjected into fertilized B6D2 oocytes. Genomic DNA was extracted from mouse tails and screened by PCR to identify transgene integration. Two lines were selected, L569 and L538, and mice were back-crossed five times to C57BL/6J mice. Mice were of a mixed background and littermates were used as control. Bladder from mice aged 1 to 24 months were examined for macroscopic lesions followed by a histopathological analysis when required. Mice were then intercrossed to obtain hetero-and homozygous mice for the transgene.