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However, the rare incidence of BBN\u2010induced upper urinary tract UC (UTUC), which originates from the same urothelium as BC, remains elusive. The scarcity of animal models of UTUC has made it challenging to study the biology of UTUC. To address this problem, we tried to establish a novel mouse model of UTUC by treating multiple mice strains and sexes with BBN. The molecular consistency between the UTUC mouse model and human UTUC was confirmed using multi\u2010omics analyses, including whole\u2010exome, whole\u2010transcriptome, and spatial transcriptome sequencing. 16S ribosomal RNA metagenome sequencing, metabolome analysis, and dietary interventions were employed to assess changes in the gut microbiome, metabolome, and carcinogenesis of UTUC. Of all treated mice, only female BALB\/c mice developed UTUC over BC. Multi\u2010omics analyses confirmed that the UTUC model reflected the molecular characteristics and heterogeneity of human UTUC with poor prognosis. 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