Referenced in: none

Automatically associated channels: Kv1.1

Title: Kv1.1-dependent control of hippocampal neuron number as revealed by mosaic analysis with double markers.

Authors: Shi-Bing Yang, Kellan D Mclemore, Bosiljka Tasic, Liqun Luo, Yuh Nung Jan, Lily Yeh Jan

Journal, date & volume: J. Physiol. (Lond.), 2012 Jun 1 , 590, 2645-58

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22411008

Abstract
Megencephaly, or mceph, is a spontaneous frame-shift mutation of the mouse Kv1.1 gene. This mceph mutation results in a truncated Kv1.1 channel α-subunit without the channel pore domain or the voltage sensor. Interestingly, mceph/mceph mouse brains are enlarged and – unlike wild-type mouse brains – they keep growing throughout adulthood, especially in the hippocampus and ventral cortex. We used mosaic analysis with double markers (MADM) to identify the underlying mechanism. In mceph-MADM6 mice with only a small fraction of neurons homozygous for the mceph mutation, those homozygous mceph/mceph neurons in the hippocampus are more abundant than wild-type neurons produced by sister neural progenitors. In contrast, neither mceph/mceph astrocytes, nor neurons in the adjacent dorsal cortex (including the entorhinal and parietal cortex) exhibited overgrowth in the adult brain. The sizes of mceph/mceph hippocampal neurons were comparable to mceph/+ or wild-type neurons. Our mosaic analysis reveals that loss of Kv1.1 function causes an overproduction of hippocampal neurons, leading to an enlarged brain phenotype.