Single gene controls development of many forms of polycystic disease

Cysts riddle a kidney from a patient with polycystic kidney disease. Credit: courtesy Yale University

A single gene is central in the development of several forms of polycystic kidney and liver disease, Yale School of Medicine researchers report in the June 19 issue of Nature Genetics.

The findings suggest manipulating activity of PKD1, the gene causing the most common form of , may prove beneficial in reducing in both liver and kidney.

"We found that these conditions are not the result of an all or nothing phenomenon," said Stefan Somlo, the C.N.H. Long Professor of Medicine and Genetics and Chief, Section of and senior author of the study. "The less PKD1 is expressed, the more cysts develop. Conversely, expressing more PKD1 can slow the process."

The most common form of this condition is called autosomal dominant polycystic kidney disease (ADPKD), a condition passed on to children from one parent affected with the disease that is found in 600,000 people in the United States alone. Two , PKD1 and PKD2, are responsible for the onset of this condition.

PKD patients also develop cysts of the liver and Somlo and colleagues had previously identified families with identical cysts found only in the liver. They found two different genes were responsible for this related condition.

The researchers wanted to know how liver-only polycystic disease was related to ADPKD. In a series of experiments using both genetically engineered mouse models and biochemical studies, they found that the activity of only one of the four genes, PKD1, controlled cyst formation in the other forms of the disease. Experiments in mice showed that modulating dosage of PKD1 could slow .

"The data suggest the exciting possibility that targeting the activity of PKD1 may be beneficial for treatment of isolated polycystic liver disease, childhood recessive polycystic kidney disease and even a subset of adult ADPKD," said Somlo.

Yale is a leader in the investigation of PKD. For instance basic scientific research conducted at Yale has been crucial in helping to identify cilia, the tiny thread-like structure that extends from a cell's surface, as a critical component in cyst forming pathways. Yale has been the home of one of the four NIH-funded national centers of excellence in PKD research since 1999. In addition, the laboratory of Craig Crews, Lewis B. Cullman Professor of Molecular, Cellular, and Developmental Biology and Professor of Chemistry and of Pharmacology, has identified a compound that has shown promise in reducing number of cysts in some mouse models of PKD.

Related Stories

Experiments point to new treatments for PKD

Apr 02, 2008

A family of small molecules called CFTR inhibitors show promising effects in slowing the progression of polycystic kidney disease (PKD), the most common genetic disease of the kidneys, according to preliminary research reported ...

A new target in polycystic kidney disease

Sep 13, 2010

In work suggesting a new approach to treating polycystic kidney disease (PKD), a leading cause of kidney failure, researchers at Children's Hospital Boston were able to block the formation of fluid-filled cysts, the hallmark ...

Recommended for you

Stress reaction may be in your dad's DNA, study finds

4 hours ago

Stress in this generation could mean resilience in the next, a new study suggests. Male mice subjected to unpredictable stressors produced offspring that showed more flexible coping strategies when under ...

More genetic clues found in a severe food allergy

5 hours ago

Scientists have identified four new genes associated with the severe food allergy eosinophilic esophagitis (EoE). Because the genes appear to have roles in other allergic diseases and in inflammation, the ...

Brain-dwelling worm in UK man's head sequenced

23 hours ago

For the first time, the genome of a rarely seen tapeworm has been sequenced. The genetic information of this invasive parasite, which lived for four years in a UK resident's brain, offers new opportunities ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.