What happens when genetic information is not correctly edited in b...( Institute for Medical Research focusse...)

Institute for Medical Research focussed their studies on ADAR2, an editing enzyme, that is found in brain and many peripheral tissues. They succeeded to impair ADAR2-mediated editing by genetic manipulation in the mouse. Now, the proteins were composed as specified exactly by the nucleotide sequence on the gene. The Heidelberg team show in the Nature study that mice making unedited gene transcripts become prone to seizures when still quite young and that they die shortly after.

The scientists then introduced a point change (mutation) into the gene for the AMPA type of glutamate receptors, a key molecule for fast communication between nerve cells. They changed the gene such that it now had the sequence for the edited version and hence, this key protein for communication between nerve cells was again produced in a correct fashion in spite of the genetically induced impairment in RNA editing. To everyone's surprise, the phenotype of the mice normalized with the mice being seizure-free and exhibiting a normal life span. These experiments show clearly that this key protein in the brain is the main target for the editing events mediated by ADAR2.

Dr. Myoko Higuchi, who has worked in Germany for 20 years and who is the first author of the Nature publication, explained that the molecular components of the editing machinery are largely unknown. Moreover, the number of genes affected by editing is also unknown. When asked if human epileptic disorders might be evoked by defects in editing she replied that while this may seem possible, it has not been properly investigated.

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Contact: Peter H. Seeburg
seeburg@mpimf-heidelberg.mpg.de
49-6221-486-495
Max-Planck-Gesellschaft
5-Jul-2000

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