A MAPP Network study: overexpression of tumor necrosis factor-α in mouse urothelium mimics interstitial cystitis

Interstitial cystitis/ bladder pain syndrome (IC/BPS) is a chronic bladder condition associated with pain and voiding dysfunction that is often regarded as a neurogenic cystitis. Patient symptoms are correlated with the presence of urothelial lesions. We previously characterized a murine neurogenic cystitis model that recapitulates mast cell accumulation and urothelial lesions, and these events were dependent upon TNF. To further explore the role of TNF in bladder inflammation and function, we generated a transgenic mouse model with chronic TNF overexpression in urothelium under the control of the uroplakin II (UPII) promoter. Transgenic mouse lines were maintained by backcross onto wild-type C57BL/6J mice, and evaluated for pelvic tactile allodynia as a measure of visceral pain, urinary function and urothelial lesions. TNF mRNA and protein were expressed at greater levels in bladders of UPII-TNF mice than wild type. UPII-TNF mice showed significantly increased urinary frequency and decreased void volume....