In Vivo Phenotypic Characterization of the Long Non-Coding RNA Kantr

Abstract

Non-coding regions of the human genome have just begun to be unraveled, and they hold the potential to be key regulators of biological mechanisms. The absence of a particular non-coding gene could be the answer to a disease that is not yet well understood. Neurological diseases are an example of those diseases that are not fully understood, because the brain is the most complex organ in the human body. Kantr is a long non-coding RNA that is expressed in the brain. Brain expression patterns using a lacz reporter gene were found to have Kantr expression in the hippocampus (C1, C2, C3), as well as the piriform cortex. Deletion of long non-coding RNA Kantr locus in mice reveled that it phenocopied human seizures. Using a device similar to the one used in humans to detect brain activity, we attached a mini-mouse size electroencephalogram (EEG) to detect mouse brain electrical activity. Through EEG recordings, we characterized the seizure activity of Kantr knockout mice. These mice had been identified as having increased seizure activity. The brain electrical activities of the Kantr knockout mice were recorded 2-5 times for 2 hours. We discovered that 89% of the Kantr knockout mice were presented with characteristic abscent seizures compared to 0% of the wild type mice. Abscent seizures are characteristic of increased spikes of electrical activity while the mouse is freezing state. Similar freezing features can be observed in a human while having an abscent seizure; thus deletions of the Kantr locus recapitulated a human phenotype.