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Publication : Transgenic mice for conditional gene manipulation in astroglial cells.

First Author  Slezak M Year  2007
Journal  Glia Volume  55
Issue  15 Pages  1565-76
PubMed ID  17823970 Mgi Jnum  J:156087
Mgi Id  MGI:4418649 Doi  10.1002/glia.20570
Citation  Slezak M, et al. (2007) Transgenic mice for conditional gene manipulation in astroglial cells. Glia 55(15):1565-76
abstractText  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 Muller 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.
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