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Scientists solve 30-year-old mystery of mutant mouse's kidney woes

Researchers seeking insights into kidney failure in human infants have located the source of a 30-year-old mystery mutation that causes similar problems in a mouse line.

Scientists have known of the mouse line's naturally occurring mutation since the early 1970s. Researchers at Washington University School of Medicine in St. Louis are the first to identify the mutated gene, allowing them to determine the mutation's effects and the origins of the disease.

"The gene codes for a protein that moves water across membranes, and we showed that the mutated form of the protein doesn't get properly distributed in the urinary system," says senior author Feng Chen, Ph.D., assistant professor of medicine. "If something similar happens in human disorders, one way to treat such diseases would be to redirect the protein to its appropriate location."

Results from Chen and his colleagues are published online in the Proceedings of the National Academy of Sciences.

Ultrasonic scans reveal fetal hydronephrosis, or enlargement of the kidney, in approximately 1 in every 100 human fetuses. The condition results from impairment of passage of urine from the kidney to the bladder. About 20 percent of those cases lead to clinical complications that, if left untreated, can include kidney failure and death.

Scientists suspect a variety of environmental and genetic factors contribute to fetal hydronephrosis. However, they frequently cannot tie it to any causative factors, making it difficult to determine how normal molecular and cellular processes in kidney development break down in infants affected by the condition.

Researchers at The Jackson Laboratory first noted the mouse line's mutation in the early 1970s when some of the mice developed enlarged bellies and died within three to four weeks of their birth. Scientists initially assumed that the mutation was causing a form of polycystic kidney disease, but a follow-up study more than a decade
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Source:Washington University School of Medicine


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