title: PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype.
abstract: A body of experimental evidence indicates that transcription and/or mRNA processing factors interacting with the polyglutamine disease gene products play crucial roles in the pathology. PQBP-1 is one of these factors and it has been shown to interact with the spinocerebellar ataxia type-1 (SCA1) disease gene product, ataxin-1. Our previous data suggested that relatively high expression of PQBP-1 in the cerebellum might explain the selective neuronal degeneration of SCA1. To further test whether PQBP-1 expression level regulates neuronal death, we generated transgenic mice of human PQBP-1 driven by a regulatory element for ubiquitous gene expression. The mice showed a late-onset and gradually progressive motor neuron disease-like phenotype, which might be related to neurogenic muscular atrophy observed in SCA1 patients. Ataxia could not be discriminated from predominant progressive weakness. Pathological examinations of the transgenic mice revealed loss of Purkinje and granular cells in the cerebellum as well as that of spinal motor neurons, corresponding to the pathology of human SCA1. These findings show that excessive action of PQBP-1 causes neuronal dysfunction and support PQBP-1 being involved in the pathology of SCA1.
authors.affiliation: Department of Molecular Therapeutics, Tokyo Metropolitan Institute for Neuroscience, 2-6, Musashi-dai, Fuchu, Tokyo 183-8526, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Okuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hattori
authors.forename: Sousuke
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ueda
authors.forename: Jorma J
authors.initials: JJ
authors.lastname: Palvimo
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kanazawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kawano
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Okazawa
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics*; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D002645:Chickens; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011689:Purkinje Cells / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D014158:Transcription, Genetic
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C119246:PQBP1 protein, human; C492272:Pqbp1 protein, mouse; D012333:RNA, Messenger