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Mouse brains deficient in neuronal PDGF receptor‐β develop normally but are vulnerable to injury
Author(s) -
Ishii Yoko,
Oya Takeshi,
Zheng Lianshun,
Gao Zhiyang,
Kawaguchi Makoto,
Sabit Hemragul,
Matsushima Takako,
Tokunaga Ayano,
Ishizawa Shin,
Hori Etsuro,
Nabeshima Yoichi,
Sasaoka Toshikuni,
Fujimori Toshihiko,
Mori Hisashi,
Sasahara Masakiyo
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03922.x
Subject(s) - excitotoxicity , biology , platelet derived growth factor receptor , tunel assay , mutant , subventricular zone , knockout mouse , gene knockout , microbiology and biotechnology , receptor , pathology , nmda receptor , immunohistochemistry , immunology , gene , medicine , genetics , growth factor , neural stem cell , stem cell
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 β subunit of PDGFR ( PDGFR‐β ) was genetically deleted in CNS neurons to elucidate the role of PDGFR‐β, particularly in the post‐natal stage. Our mutant mice reached adulthood without apparent anatomical defects. In the mutant brain, immunohistochemical analyses showed that PDGFR‐β detected in neurons and in the cells in the subventricular zone of the lateral ventricle in wild‐type mice was depleted, but PDGFR‐β 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‐β expressed in neurons protects them from cryogenic injury and NMDA‐induced excitotoxicity.