Knockout Mice Help Researchers Find Ways To Knockout Incontinence

April Flowers for – Your Universe Online

Millions suffer from overactive bladder or incontinence, and now help might be on the way. A new study, led by Harvard Medical School, reveals that the epithelium, a thin layer of cells lining the surface of the bladder, is able to sense how full the bladder is through the action of a family of proteins called integrins. The cells of the epithelium stretch and become thinner as the bladder fills. This activates the integrins, causing them to send the information to nerves and other cells in the bladder.

The findings of this study, published online in the FASEB Journal, may one day help researchers design drugs that target this mechanism to treat conditions like incontinence and overactive bladder — common, serious problems affecting millions of people.

“I am very hopeful that as we learn more about how the bladder senses fullness and conveys that information to the nerves and the muscles which control our ability to urinate, that this greater understanding and knowledge will lead to new treatments,” said Warren G. Hill, Ph.D., a researcher from the Department of Medicine at Beth Israel Deaconess Medical Center and Harvard Medical School.

“It is extremely important that we do this as quickly as possible, since there are millions of people who suffer enormously from the anguish of bladder pain, incontinence and constant feelings of needing to go. I am optimistic these new insights into the role of integrins will begin the process of discovering important new drug targets which will dramatically improve the quality of life for many of these people.”

The research team tested two groups of mice. One group were genetically modified to be missing an important member of the integrin family in the epithelium, while the second group of mice was normal. Both groups of mice had normal appearing bladders, but the group without the integrin protein had very little bladder control. When the researchers tested the bladders of the integrin knockout mice, they found the bladders were constantly squeezing and very overactive. They also found that the mice overfilled their bladders and took much longer to urinate than the normal mice.

Most current drug treatments target proteins in the muscle surrounding the bladder for overactive bladder problems. The findings of this study demonstrate that it might be possible to design drugs that target sensory proteins in the epithelium.

“No one wants to pee in his or her pants,” said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, “but the reality is that bladder problems — incontinence, frequency and pain – affect more people than we realize. This report offers hope that new drugs targeting the bladder’s epithelium will succeed when current drugs fail.”