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Severe congenital disorder successfully treated in a mouse model for the first time
Date:12/22/2011

ached to the body's proteins or in some cases, are not attached at all. The lack of oligosaccharide chains leads to impairment of neurological, growth and organ development. The disorder only manifests if the baby inherits a mutated gene from both the mother and the father. The parents, who each carry one mutated and one "healthy" copy of the gene, do not exhibit any symptoms.

Mice take up mannose in drinking water

The mouse model developed by Prof. Krner and his team is characterized by mutations in the Phosphomannomutase 2 gene and demonstrates reduced enzyme activity, comparable to CDG-Ia in man. In their current study, the scientists exploited the ability of mannose to cross the placental barrier. This means that if the pregnant mouse takes up mannose, it also reaches the embryos in the uterus.

"One week prior to mating, we began giving the female mice mannose with their drinking water," explained biochemist Prof. Krner. The additional mannose supply up to birth increased the mannose levels in the embryos' blood. "The mice were born without defects and also after they were born, developed without any symptoms of the disorder, even if they no longer took up any mannose," Krner added. The successful studies performed by the Heidelberg University Hospital researchers clearly show the key role played by the supply of proteins with sugar chains during embryonic development.

New therapeutic approach

"Clinical studies in the U.S. and Germany have already been performed in which children with CDG-Ia were given mannose after they were born, either orally or by intravenous infusion. Unfortunately, these attempts have not been successful," explained Dr. Christian Thiel, head of the laboratory. "This means that the critical point at which it is possible to influence development must be during development in the uterus." For women with a risk of CDG-Ia, administering mannose during pregnancy may serve as a new therap
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Contact: Prof. Dr. rer. nat. Christian Krner
christian.koerner@med.uni-heidelberg.de
49-622-156-39993
University Hospital Heidelberg
Source:Eurekalert  

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