title: Kv1.1-dependent control of hippocampal neuron number as revealed by mosaic analysis with double markers.
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.
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology, University of California–San Francisco, San Francisco, CA, USA.
authors.forename: Shi-Bing
authors.initials: SB
authors.lastname: Yang
authors.forename: Kellan D
authors.initials: KD
authors.lastname: Mclemore
authors.forename: Bosiljka
authors.initials: B
authors.lastname: Tasic
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.forename: Yuh Nung
authors.initials: YN
authors.lastname: Jan
authors.forename: Lily Yeh
authors.initials: LY
authors.lastname: Jan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D005260:Female; D051662:Kv1.1 Potassium Channel / Q000502:physiology*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000473:pathology*
chemical_list: D051662:Kv1.1 Potassium Channel