title: Chorein deficiency leads to upregulation of gephyrin and GABA(A) receptor.
abstract: Chorea-acanthocytosis (ChAc) is a hereditary neurodegenerative disorder caused by loss of function mutations in the VPS13A gene encoding chorein. Recently, using a gene-targeting technique to delete exons 60-61, we produced a ChAc-model mouse that corresponds to a human disease mutation. In this study, a comparative microarray analysis of gene expression in the striatum revealed an increased level of gephyrin gene expression in the ChAc-model mice compared with wild type mice. Since gephyrin is known as a GABA(A) receptor-anchoring protein, we compared the protein-level expression and localization of gephyrin and the GABA(A) receptor alpha1 (GABRA1) and gamma2 (GABRG2) subunits. Gephyrin and GABRG2 immunoreactivities in the striatum and hippocampus of the ChAc-model mice were significantly higher than those in the wild types. Our results suggest that chorein functional loss may lead to a compensatory upregulation of gephyrin and GABRG2 in the pathologic condition in ChAc.
authors.affiliation: Department of Psychiatry, Kagoshima University, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kurano
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Mio
authors.initials: M
authors.lastname: Ichiba
authors.forename: Mieko
authors.initials: M
authors.lastname: Matsuda
authors.forename: Emiko
authors.initials: E
authors.lastname: Mizuno
authors.forename: Maiko
authors.initials: M
authors.lastname: Kato
authors.forename: Shuji
authors.initials: S
authors.lastname: Izumo
authors.forename: Akira
authors.initials: A
authors.lastname: Sano
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D021122:Protein Subunits / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D015854:Up-Regulation; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; C546240:GABRA1 protein, human; C546279:GABRG2 protein, human; C546241:Gabra1 protein, mouse; C546280:Gabrg2 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D011963:Receptors, GABA-A; D033921:Vesicular Transport Proteins; C497828:Vps13a protein, mouse; C073441:gephyrin