Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice

Jan Winchenbach; Tim Düking; Stefan A Berghoff; Sina K Stumpf; Swen Hülsmann; Klaus-Armin Nave; Gesine Saher

doi:10.12688/f1000research.10509.1

Inducible targeting of CNS astrocytes in Aldh1l1-CreERT2 BAC transgenic mice

F1000Res. 2016 Dec 30:5:2934. doi: 10.12688/f1000research.10509.1. eCollection 2016.

Authors

Jan Winchenbach¹, Tim Düking¹, Stefan A Berghoff¹, Sina K Stumpf¹, Swen Hülsmann², Klaus-Armin Nave³, Gesine Saher¹

Affiliations

¹ Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
² Clinic for Anesthesiology, Research Group Central Respiratory Control, University Medical Center Göttingen, Experimental Neuroanesthesiology, Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
³ Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.

Abstract

Background: Studying astrocytes in higher brain functions has been hampered by the lack of genetic tools for the efficient expression of inducible Cre recombinase throughout the CNS, including the neocortex. Methods: Therefore, we generated BAC transgenic mice, in which CreERT2 is expressed under control of the Aldh1l1 regulatory region. Results: When crossbred to Cre reporter mice, adult Aldh1l1-CreERT2 mice show efficient gene targeting in astrocytes. No such Cre-mediated recombination was detectable in CNS neurons, oligodendrocytes, and microglia. As expected, Aldh1l1-CreERT2 expression was evident in several peripheral organs, including liver and kidney. Conclusions: Taken together, Aldh1l1-CreERT2 mice are a useful tool for studying astrocytes in neurovascular coupling, brain metabolism, synaptic plasticity and other aspects of neuron-glia interactions.

Keywords: Astrocyte; Bergman glia; inducible Cre recombinase; neuroscience; tamoxifen.

Grants and funding

This work was funded by the Deutsche Forschungsgemeinschaft (SFB/TR43 to KAN, SPP1757 SA 2014/2-1 to GS), by an ERC advanced grant to KAN, and by the CNMPB to SH.