Mouse brains deficient in neuronal PDGF receptor-beta develop normally but are vulnerable to injury.
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.
Ishii
Yoko
Y
Department of Pathology, Faculty of Medicine, University of Toyama, Toyama, Japan.
Oya
Takeshi
T
Zheng
Lianshun
L
Gao
Zhiyang
Z
Kawaguchi
Makoto
M
Sabit
Hemragul
H
Matsushima
Takako
T
Tokunaga
Ayano
A
Ishizawa
Shin
S
Hori
Etsuro
E
Nabeshima
Yo-ichi
Y
Sasaoka
Toshikuni
T
Fujimori
Toshihiko
T
Mori
Hisashi
H
Sasahara
Masakiyo
M
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
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