Exploding Frog Eggs And People With Rare Disorder Help Researchers Unravel Mysteries Of Water Regulation In Humans: Discovery May Lead To Treatments For Kidney Disorders

"This is the first study to show that the protein called aquaporin-1 has a clear role in the normal function of the kidney," says Landon King, M.D., an assistant professor of pulmonary medicine and lead author of the study. "Aquaporin-1 is required for the kidney to concentrate urine, a fundamental process for all mammals."

The study showed that individuals deficient in the protein have a limited ability to concentrate urine, or, in other words, to reabsorb water through their kidneys. This is essential for maintaining healthy water levels in the body. The finding may help doctors develop treatments for diseases such as diabetes insipidus, an ailment that inhibits reabsorption of water causing frequent urination and emaciation.

Until 10 years ago, scientists didn’t know how cells regulate water, surprising since this task is fundamental to life. Water makes up 70 percent of the human body, and while certain cells need to absorb water quickly, other cells are relatively impermeable to water. Then, roughly 10 years ago, Peter Agre, M.D., a Hopkins professor of biochemistry, stumbled upon an unknown protein lodged in the plasma membrane of red blood cells and kidney tubules. After expressing the protein in frogs’ eggs, the scientists discovered that the eggs exploded when immersed in water because they absorbed the liquid much faster than normal. Agre named the protein aquaporin because it acted as a pore or water channel through which fluids flow in and out of the membrane.

Since the exploding frog eggs, scientists have identified 10 aquaporin proteins in the more water-permeable parts of the body -- the moist surface tissues of the alveoli in the lung, tubules in the kidneys, and tear glands, to name a few. But researchers wondered whether they could find any people with missing or defective aquaporin proteins. To accomplish their goal, Agre and pulmonologist Landon King turned to international blood banks and identified six families with a deficiency in aquaporin-1(AQP1). After tracking down two of the individuals – a 37-year-old woman from North Carolina and a 57-year old woman from France – and depriving them of water for 24 hours under close monitoring, King determined that they have a limited ability to concentrate urine.

Surprisingly however, the individuals did not have more serious health issues, since AQP1 is involved in transporting water not only in the kidneys but in a number of other organs, including the lungs and pancreas. "We believe that these people have some form of compensation that helps to mitigate the severity of the problem and most likely developed these compensatory mechanisms in the womb," says King. "If a person suddenly developed a deficiency in AQP1 without these compensatory mechanisms, they are much more likely to have severe health problems."

In addition to King and Agre, other authors include Michael Choi, M.D., from Johns Hopkins, as well as Jean-Pierre Cartron, Ph.D., and Pedro Fernandez, M.D., from the University of Pennsylvania. The National Institutes of Health, the Cystic Fibrosis Foundation and the National Center for Research Sources funded the study.