Researchers studying mutant mice report in Nature Genetics that they have identified the precise mechanism underlying the development of membranoproliferative glomerulonephritis (MPGN). MPGN is a common cause of chronic kidney failure in humans.
Chronic MPGN occurs when the body's immune system attacks the glomeruli -- the subunits of the kidney that filter the blood -- resulting in their progressive destruction. There were hints from studies of both animals and humans that MPGN might result from an uncontrolled activation of part of the immune system that normally helps to eliminate foreign cells or toxins. Attempts to prove this, however, have been inconclusive.
Marina Botto and colleagues generated mice with a genetic deficiency for factor H, whose normal role is to act as a brake on part of the immune system. These mice developed glomerulonephritis. When they examined mice lacking both factor H and another protein called factor B, which has an opposing role (acting as an accelerator rather then a brake), they found no evidence of kidney disease. This ‘rescue’ confirms that glomerulonephritis in mice is caused by uncontrolled activity of certain components of the immune system.
In a related News and Views article to be published in the same issue, Thomas Welch suggests that future work on MPGN in humans will focus on the ways in which infections or environmental insults might work together with uncontrolled immune activity to trigger this disease.
Dr. Marina Botto
Imperial College, London, UK
Tel: +44 20 8383 2316; E-mail: firstname.lastname@example.org
News & Views contact:
Dr. Thomas R. Welch
Upstate Medical University, Syracuse, NY, USA
Tel: +1 315 464 5451; E-mail: email@example.com
Articles can be accessed online at ng912 and ng933.
(C) Nature Genetics press release.
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