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Headlines Published on 01 August 2007

Title European researchers help discover gene against kidney disease

Researchers based at the European Molecular Biology Laboratory (EMBL) in Germany and the University of Michigan (US) have discovered a gene that protects us against a serious kidney disease. The current online issue of Nature Genetics reports that mutations in the gene cause nephronopthisis (NPHP) in humans and mice. The disease causes kidney degeneration during childhood, which results in kidney failure requiring organ transplantation. The work, which involves a combination of mice and patient studies, has led to a greater understanding of the root cause that will help develop new and effective non-invasive therapies.

Currently, the disease NPHP leads to kidney failure, requiring organ transplantation. © Matt+
Currently, the disease NPHP leads to kidney failure, requiring organ transplantation.
The role of the kidneys is to help rid the body of harmful waste products. Diseases that affect this fundamental function are very serious, and up till now, poorly understood. NPHP is a disease that sets in at early childhood, causing the kidneys to degenerate and shrink, often leading to renal failure before the age of thirty. To date, the only hope for a patient suffering from NPHP has been a kidney transplant. Using new mouse models, Mathias Treier and his team at EMBL have begun to shed light onto the underlying molecular mechanisms of NPHP, paving the way for new treatments.

‘Our mice show striking similarities with NPHP patients,’ claims Mathias Treier, leader of the EMBL group. ‘Very early on in their lives, their kidney cells start to die and the mice develop all the characteristic symptoms of the disease. It is the first time that a mouse model has revealed increased cell death as the mechanism underpinning kidney degeneration in NPHP. The genetic cause is a mutation in a gene called GLIS2.’

The normal role of GLIS2 is to prevent cell death in the adult kidney. This is achieved by shutting down genes that initiate cell death; they are only required during the development of the organ. A mutation interfering with GLIS2 function reactivates these harmful genes, with the result that large numbers of kidney cells die. The organ shrinks, and changes in its architecture occur that affect the ability of the kidney to function normally.

To ascertain if GLIS2 has the same effect in humans, Friedhelm Hildebrandt and his team at the University of Michigan carried out genetic screening of patients suffering from NPHP. They discovered that some patients carried mutations in the same GLIS2 gene, like the mouse model, confirming that GLIS2 is a crucial player in NPHP in humans.

‘This is an excellent example of how combining basic research with clinical studies can help uncover mechanisms of human disease,’ states Henriette Uhlenhaut, who undertook the research in Treier’s lab. ‘The next step will be to translate the insights gained into new therapeutic approaches to develop alternatives to kidney transplantations. With GLIS2 we have already identified one promising candidate drug target and our mouse model will help us find many others.’

More information:

  • EMBL
  • 'Scientists find gene causing type 2 diabetes'

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