Genomic imprinting is the epigenetic marking of a subset of genes which results in monoallelic or predominant expression of one of the two parental alleles according to their parental origin. In my previous work, I discovered the imprinted expression of the Kcnk9 gene in mice and humans. Kcnk9 is a member of the two-pore (2P)-domain K+ channel family and encodes for the potassium channel protein TASK-3. This family of K+ channels was already shown to play a critical role in both cell apoptosis and tumorigenesis. Furthermore, a Kcnk9 mutation in a rat strain which represents the genetic model of absence epilepsy along with the highest expression in brain indicates that Kcnk9 plays an important role in the central nervous system. The specific aim of this project is to investigate the function of the imprinted gene Kcnk9 by gene targeting in the mouse. The research plan includes a complete characterization of imprinted expression of Kcnk9 by in situ hybridization and allelic expression analysis. The Kcnk9 knock-out will be investigated whether there are significant effects in developmental and physiological processes. Furthermore, the Kcnk9 deficient mice will be examined in terms of neurodevelopmental defects.
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