U.S. Department of Health and Human Services

Mouse Model Provides New Insight into Bladder Control

​Recent research has identiied a protein, β1-integrin, as having an essential role in bladder control in mice. The inner surface of the urinary tract is lined with epithelial tissue, or urothelium, which functions as a barrier to bacteria, environmental carcinogens, toxins, and the numerous and variable waste products in urine. The bladder is a balloon-shaped organ that stores and releases urine. The bladder muscle relaxes and stretches when it ills with urine, and it squeezes when it is time to urinate. As the bladder ills with urine, nerves carry signals about its change in shape and stretching—mechanosensory signals—to let the brain know when the bladder is full. Nerves also carry signals from the brain to tell the bladder when it is time to urinate. Improperly operating signals can lead to one of several conditions, including urinary frequency, urinary urgency, and urinary incontinence. Urinary frequency is an excessive number of urinations. Urinary urgency is the sudden, strong need to urinate immediately. Urinary incontinence (UI) is the unintentional leakage of urine.

Scientists have studied the ability of mice to maintain bladder control. A group of mice was genetically modiied to no longer produce β1-integrin in the urothelium; a second group served as a normal population. β1-integrin, a member of a family of proteins called integrins, helps to anchor cells to the surrounding tissue. Surprisingly, the bladders of mice lacking the integrin were found to be normal in appearance. However, in contrast to normal mice, mice lacking β-1 integrin were found to have several abnormal bladder conditions that may relect urinary incontinence, urinary frequency, and urinary urgency, and their bladders illed beyond normal limits before triggering urination. The study’s indings in mice strongly suggest that loss of β1-integrin signaling in urothelium results in abnormal mechanosensory activity; information about the bladder’s shape and level of fullness is not properly relayed or triggers improper responses. Future studies could explore whether people with urinary frequency, urinary urgency, and urinary incontinence also have abnormal integrin signaling in their urothelium. If the human bladder works similarly, then loss of normal urothelium mechanosensory signals due to disease or injury may lead to some forms of urinary frequency, urinary urgency, and urinary incontinence in people, and treatments based on this knowledge may follow.

Kanasaki K, Yu W, von Bodungen M, et al. Loss of
β1‑integrin from urothelium results in overactive bladder
and incontinence in mice: a mechanosensory rather than
structural phenotype. FASEB J 27: 1950-1961, 2013.