Temporal regulation of Cre recombinase activity in neural stem cells.
Neural stem cells are known to give rise to distinct subtypes of neurons and glial cells over time by changing their competency. However, precise characterization of neural stem cells at various developmental stages remains to be performed. For such analysis, a tool to manipulate neural stem cells at different time points is necessary. Here, we generated transgenic mice that express Cre-ER(T2) in the ventricular zone of the developing nervous system under the control of the nestin promoter and enhancer (Nes-CreER(T2)). In mice expressing Cre-ER(T2) at appropriate levels, Cre recombinase activity was mostly inactive but efficiently activated by tamoxifen within 1 day. When such mice were crossed with the ROSA-26 or Z/EG reporter mice, neural stem cells were permanently labeled after administration of tamoxifen. Thus, Nes-CreER(T2) mice offer a powerful tool to manipulate neural stem cells genetically at desired time points.
Imayoshi
Itaru
I
Institute for Virus Research, Kyoto University, Kyoto, Japan.
Ohtsuka
Toshiyuki
T
Metzger
Daniel
D
Chambon
Pierre
P
Kageyama
Ryoichiro
R
D000818:Animals; D001921:Brain / Q000166:cytology; D003433:Crosses, Genetic; D004742:Enhancer Elements, Genetic; D005260:Female; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting / Q000379:methods*; D017930:Genes, Reporter; D019426:Integrases / Q000235:genetics*; D007381:Intermediate Filament Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009420:Nervous System / Q000196:embryology; D064231:Nestin; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D013234:Stem Cells; D013629:Tamoxifen / Q000494:pharmacology
C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011506:Proteins; D022661:RNA, Untranslated; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases