Inducible site-specific recombination in neural stem/progenitor cells.
To establish a genetic tool for manipulating the neural stem/progenitor cell (NSC) lineage in a temporally controlled manner, we generated a transgenic mouse line carrying an NSC-specific nestin promoter/enhancer expressing a fusion protein encoding Cre recombinase coupled to modified estrogen receptor ligand-binding domain (ER(T2)). In the background of the Cre reporter mouse strain Rosa26(lacZ), we show that the fusion CreER(T2) recombinase is normally silent but can be activated by the estrogen analog tamoxifen both in utero, in infancy, and in adulthood. As assayed by beta-galactosidase activity in embryonic stages, tamoxifen activates Cre recombinase exclusively in neurogenic cells and their progeny. This property persists in adult mice, but Cre activity can also be detected in granule neurons and Bergmann glia at the anterior of the cerebellum, in piriform cortex, optic nerve, and some peripheral ganglia. No obvious Cre activity was observed outside of the nervous system. Thus, the nestin regulated inducible Cre mouse line provides a powerful tool for studying the physiology and lineage of NSCs.
Chen
Jian
J
Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA.
Kwon
Chang-Hyuk
CH
Lin
Lu
L
Li
Yanjiao
Y
Parada
Luis F
LF
D053687:Adult Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D009420:Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D064231:Nestin; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases