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'Knockout' mouse may lead to major understanding of human kidney disorder

A basic science advance has provided a major clue to the possible cause and treatment of IgA nephropathy, a kidney disorder that affects hundreds of millions of people throughout the world. The advance, appearing in the September issue of Nature Medicine, represents what may be one of the most promising applications of "gene knockout" technology to date.

The study was conducted by scientists at the Heritable Disorders Branch of the National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), and Baylor College of Medicine. The finding builds upon a previous advance, the development of mice strains lacking the gene for a substance known as uteroglobin. In that study, the resultant mice were found to have malfunctioning kidneys due to clogged glomeruli, the kidney's filtering apparatus.

In the Nature Medicine article, the group has since determined that this kidney malfunction closely mimics the human disease, IgA nephropathy. The researchers also prevented the disorder in the mice by supplying the deficient animals with the uteroglobin normally made by the non-functioning gene.

"This mouse model matches the human form of IgA nephropathy very closely," said NICHD Director Duane Alexander, M.D. "It has provided us with very specific strategies for possibly determining the cause of the human condition and ultimately designing a treatment for it."

IgA nephropathy is the most common primary kidney glomerular disease in the world. In the U.S., more than 3,000 cases occur each year, explained the study's first author, Feng Zheng, M.D., who was at the NICHD when the study was conducted. However, in other areas, such as Japan, parts of Europe, and Australia, the disease may cause 35-40 percent of all primary glomerulopathies.

Briefly, IgA (Immunoglobin A) nephropathy results from deposits of IgA inside the kidneys. (IgA is an antibody, an immune system p
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Contact: Robert Bock
rb96a@nih.gov
301-496-5133
NIH/National Institute of Child Health and Human Development
30-Aug-1999


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