UT Southwestern researchers discover link that could aid in treatment of kidney cyst diseases

DALLAS March 15, 2004 Researchers at UT Southwestern Medical Center at Dallas have uncovered a link between two cyst-forming diseases that affect the kidneys, a finding that could lead to treatments for both a rare form of diabetes and a common kidney disease.

"We discovered that the formation of kidney cysts in both maturity-onset diabetes of the young type 5 (MODY5) and autosomal recessive polycystic disease is related to the same gene abnormality. It was a surprise to find this link, as it was not suspected that these two diseases were linked together," said Dr. Peter Igarashi, chief of nephrology at UT Southwestern and senior author of the study, which appears in today's issue of The Journal of Clinical Investigation.

"This finding provides a framework for further investigation. The goal is to understand disease mechanisms, and any time you can find a link between two diseases, it provides an opportunity to better understand the mechanisms involved," Dr. Igarashi said.

MODY5 is a rare inherited form of diabetes caused by mutations of HNF-1, a protein that regulates gene expression. The disease is associated with congenital abnormalities of the kidneys, a condition resulting in large, fluid-filled cysts that lead to kidney failure.

Since it is largely unknown what triggers these cysts to form, Dr. Igarashi and his colleagues used a mouse model to express a mutant form of HNF-1 similar to the form in humans with MODY5. These mice also developed kidney cysts and eventually experienced kidney failure.

The researchers then looked for changes in the expression of other genes involved in cyst formation. Surprisingly, they found the expression of the PKHD1 gene was markedly decreased in the mutated mice. Mutations of PKHD1 cause autosomal recessive polycystic kidney disease, a common genetic cystic disease that affects between one in 10,000 to 40,000 babies and is often fatal in the first month of life. In addition, they found

Contact: Scott Maier
UT Southwestern Medical Center

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