title: Mouse brains deficient in neuronal PDGF receptor-beta develop normally but are vulnerable to injury.
abstract: Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are widely expressed in the mammalian CNS, though their functional significance remains unclear. The corresponding null-knockout mutations are lethal. Here, we developed novel mutant mice in which the gene encoding the beta subunit of PDGFR (PDGFR-beta) was genetically deleted in CNS neurons to elucidate the role of PDGFR-beta, particularly in the post-natal stage. Our mutant mice reached adulthood without apparent anatomical defects. In the mutant brain, immunohistochemical analyses showed that PDGFR-beta detected in neurons and in the cells in the subventricular zone of the lateral ventricle in wild-type mice was depleted, but PDGFR-beta detected in blood vessels remained unaffected. The cerebral damage after cryogenic injury was severely exacerbated in the mutants compared with controls. Furthermore, TdT-mediated dUTP-biotin nick end labeling (TUNEL)-positive neuronal cell death and lesion formation in the cerebral hemisphere were extensively exacerbated in our mutant mice after direct injection of NMDA without altered NMDA receptor expression. Our results clearly demonstrate that PDGFR-beta expressed in neurons protects them from cryogenic injury and NMDA-induced excitotoxicity.
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Toyama, Toyama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ishii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oya
authors.forename: Lianshun
authors.initials: L
authors.lastname: Zheng
authors.forename: Zhiyang
authors.initials: Z
authors.lastname: Gao
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Hemragul
authors.initials: H
authors.lastname: Sabit
authors.forename: Takako
authors.initials: T
authors.lastname: Matsushima
authors.forename: Ayano
authors.initials: A
authors.lastname: Tokunaga
authors.forename: Shin
authors.initials: S
authors.lastname: Ishizawa
authors.forename: Etsuro
authors.initials: E
authors.lastname: Hori
authors.forename: Yo-ichi
authors.initials: Y
authors.lastname: Nabeshima
authors.forename: Toshikuni
authors.initials: T
authors.lastname: Sasaoka
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujimori
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mori
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sasahara
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000254:growth & development* / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology*; D001925:Brain Damage, Chronic / Q000235:genetics / Q000473:pathology; D017931:DNA Primers; D005615:Freezing; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D016202:N-Methylaspartate / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000235:genetics; D064231:Nestin; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000172:deficiency* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016202:N-Methylaspartate; D020797:Receptor, Platelet-Derived Growth Factor beta