RRC ID |
43298
|
著者 |
Fujimori A, Yaoi T, Ogi H, Wang B, Suetomi K, Sekine E, Yu D, Kato T, Takahashi S, Okayasu R, Itoh K, Fushiki S.
|
タイトル |
Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in humans.
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ジャーナル |
Biochem Biophys Res Commun
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Abstract |
Microcephaly is a malformation associated with in utero exposed atomic bomb survivors and can be induced in mice by fetal exposure to ionizing radiation (IR). The pathogenesis of IR-induced microcephaly, however, has not been fully understood. Our analyses of high-coverage expression profiling (HiCEP) demonstrated that the abnormal spindle-like microcephaly associated gene (ASPM) was down-regulated in irradiated human diploid fibroblasts. ASPM was recently reported as the causative gene for MCPH-5, the most common type of congenital microcephaly in humans. Here, we show that the expression of the Aspm gene was significantly reduced by IR in various human and murine cells. Additionally, Aspm was found downregulated in the irradiated fetal mouse brain, particularly in the ventricular zones. A similar suppression was observed in the irradiated neurosphere cultures. This is the first report suggesting that the suppression of Aspm by IR could be the initial molecular target leading to the future microcephaly formation.
|
巻・号 |
369(3)
|
ページ |
953-7
|
公開日 |
2008-5-9
|
DOI |
10.1016/j.bbrc.2008.02.149
|
PII |
S0006-291X(08)00415-4
|
PMID |
18331833
|
MeSH |
Animals
Brain / metabolism
Brain / radiation effects*
Cell Line
Down-Regulation
Gene Expression / radiation effects*
Humans
Mice
Mice, Inbred Strains
Microcephaly / genetics*
Nerve Tissue Proteins / analysis
Nerve Tissue Proteins / genetics*
Neurons / chemistry
Neurons / metabolism
Neurons / radiation effects
RNA, Messenger / analysis
RNA, Messenger / metabolism
Radiation Injuries, Experimental / genetics*
Radiography
Stem Cells / chemistry
Stem Cells / diagnostic imaging
Stem Cells / metabolism
|
IF |
2.985
|
引用数 |
18
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
|