Abstract:
:Astrocytes are thought to exert diverse functions in the brain, but it has been difficult to prove this in vivo because of a scarcity of tools to manipulate these cells. Here, we report the generation of new transgenic mouse lines that allow for conditional gene ablation in astrocytes using the tamoxifen- (TAM-) inducible CreER(T2)/loxP system and bacterial artificial chromosome (BAC)-based transgenesis. In adult transgenic mice, where CreER(T2) expression is driven by the promoter of the sodium-dependent glutamate/aspartate transporter (Glast/Slc1a3) or of connexin 30 (Cx30/Gjb6), intraperitoneal TAM-injection induced Cre-mediated recombination in astroglial cells throughout the brain. Targeting efficacies varied in a region-specific manner from 20 to 90% as indicated by enzyme-based reporter lines and immunohistochemical staining. In addition, the Glast-line allowed to target retinal Müller cells and adult neural stem/progenitor cells in neurogenic regions of the adult brain. Transgenic mice expressing CreER(T2) under the control of the apolipoprotein e (ApoE) or aquaporin 4 (Aqp4) promoter showed inducible recombination in different areas of the central nervous system (CNS) albeit at low levels. Transgenic lines showed TAM-induced recombination in specific peripheral organs. These new mouse lines should help to further explore the relevance of astrocytes for brain function, as well as their contribution to pathological conditions because of aging, disease or injury.
journal_name
Gliajournal_title
Gliaauthors
Slezak M,Göritz C,Niemiec A,Frisén J,Chambon P,Metzger D,Pfrieger FWdoi
10.1002/glia.20570subject
Has Abstractpub_date
2007-11-15 00:00:00pages
1565-76issue
15eissn
0894-1491issn
1098-1136journal_volume
55pub_type
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