title: Sodium channel beta4 subunit: down-regulation and possible involvement in neuritic degeneration in Huntington's disease transgenic mice.
abstract: Sodium channel beta4 is a very recently identified auxiliary subunit of the voltage-gated sodium channels. To find the primarily affected gene in Huntington's disease (HD) pathogenesis, we profiled HD transgenic mice using a high-density oligonucleotide array and identified beta4 as an expressed sequence tag (EST) that was significantly down-regulated in the striatum of HD model mice and patients. Reduction in beta4 started at a presymptomatic stage in HD mice, whereas other voltage-gated ion channel subunits were decreased later. In contrast, spinal cord neurons, which generate only negligible levels of expanded polyglutamine aggregates, maintained normal levels of beta4 expression even at the symptomatic stage. Overexpression of beta4 induced neurite outgrowth in Neuro2a cells, and caused a thickening of dendrites and increased density of dendritic spines in hippocampal primary neurons, indicating that beta4 modulates neurite outgrowth activities. These results suggest that down-regulation of beta4 may lead to abnormalities of sodium channel and neurite degeneration in the striatum of HD transgenic mice and patients with HD.
authors.affiliation: Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Oyama
authors.forename: Haruko
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Naoaki
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Celine
authors.initials: C
authors.lastname: Becquet
authors.forename: Yoko
authors.initials: Y
authors.lastname: Machida
authors.forename: Kumi
authors.initials: K
authors.lastname: Kaneko
authors.forename: Chiharu
authors.initials: C
authors.lastname: Uchikawa
authors.forename: Taishi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Masaru
authors.initials: M
authors.lastname: Kurosawa
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Ikeda
authors.forename: Akira
authors.initials: A
authors.lastname: Tamaoka
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000235:genetics; D019295:Computational Biology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D016208:Databases, Factual; D015536:Down-Regulation / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology*; D016501:Neurites / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000096:biosynthesis*; D062585:Voltage-Gated Sodium Channel beta-4 Subunit
chemical_list: C497241:Scn4b protein, mouse; D015222:Sodium Channels; D062585:Voltage-Gated Sodium Channel beta-4 Subunit; D004247:DNA