Science Daily —
Researchers from the European Molecular Biology Laboratory (EMBL) and
the University of Michigan have discovered a gene that protects us
against a serious kidney disease. In Nature Genetics they report that
mutations in the gene cause nephronopthisis (NPHP) in humans and mice.
NPHP is a disease marked by kidney degeneration during childhood that
leads to kidney failure requiring organ transplantation. The insights
might help develop effective, noninvasive therapies.
The kidneys are the organs that help our body
dispose of potentially harmful waste. Diseases that affect this
fundamental function are very serious but so far only poorly
understood. NPHP is such a disease; it causes the kidneys to degenerate
and shrink starting early on in childhood often leading to renal
failure before the age of 30. So far, kidney transplantation in early
age has been the only way to save patients suffering from NPHP. With a
new mouse model Mathias Treier and his group at EMBL have shed new
light on the molecular mechanisms underlying NPHP opening up novel ways
to treat the disease. "Our mice show striking similarities with
NPHP patients," says Mathias Treier, group leader at EMBL. "Very early
on in their lives their kidney cells start to die and the mice develop
all the characteristic disease symptoms. It is the first time that a
mouse model reveals increased cell death as the mechanism underpinning
kidney degeneration in NPHP. The genetic cause is a mutation in a gene
called GLIS2." GLIS2 normally prevents cell death in the adult
kidney. It does so by shutting down genes that initiate cell death and
that are only required during the development of the organ. A mutation
interfering with GLIS2 function reactivates these harmful genes the
result being that large numbers of kidney cells die. The organ shrinks
and changes in its architecture occur which affect normal kidney
function. To find out if GLIS2 has the same effect in humans
Friedhelm Hildebrandt and his team at the University of Michigan
carried out a genetic screen of patients suffering from NPHP. They
found that like the mouse model some patients carried mutations in the
same GLIS2 gene, confirming that GLIS2 is a crucial player in NPHP also
in humans. "This is an excellent example of how combining basic
research with clinical studies can help uncovering mechanisms of human
disease," says Henriette Uhlenhaut who carried out 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."
Note: This story has been adapted from a news release issued by European Molecular Biology Laboratory.
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