Neue transgene Mausmodelle zur Untersuchungder Rolle von Astrozyten bei der Synaptogenese in vivo

• Antragsteller: Dr. Frank W. Pfrieger
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2004 bis 2009
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5430051

• Erstellungsjahr: 2011

Zusammenfassung der Projektergebnisse

A major question in neuroscience is whether synaptic connections develop and function autonomously or whether they require the help of glial cells, namely synapse-surrounding astrocytes. To address this topic in vivo, we proposed to generate new transgenic mouse lines that allow for conditional gene ablation in astrocytes using site-specific recombination (Cre/loxP system) and bacterial artificial chromosome-based transgenesis. We selected four distinct astrocyte-specific promoters to control expression of an inducible version of Cre recombinase (CreERT2) and generated a total of 15 mouse lines. Their characterization revealed that two of these lines (Glast-CreERT2 and Cx30-CreERT2) allow for gene manipulation in partially overlapping populations of astroglial cells in the central nervous system and in the retina. Importantly, our lines also allow to modify precursor cells in the developing and adult brain. Our transgenic mice have become a widely used tool to study precursor cells and astrocytes in vivo.

Projektbezogene Publikationen (Auswahl)

• Transgenic mice for conditional gene manipulation in astroglial cells. Glia, Vol. 55. 2007, Issue 15, pp. 1565-1576.
  Slezak M., Goritz C., Niemiec A., Frisen J., Chambon P., Metzger D., Pfrieger F.W.
  
• Origin of new glial cells in intact and injured adult spinal cord. Cell Stem Cell, Vol. 7. 2010, Issue 4, pp. 470–482.
  Barnabé-Heider F., Göritz C., Sabelström H., Takebayashi H., Pfrieger F.W., Meletis K., Frisén J.
  
• RBPJkappa-dependent signalling is essential for longterm maintenance of neural stem cells in the adult hippocampus. Journal of Neuroscience, Vol. 30. 2010, Issue 41, pp. 13794-13807.
  Ehm O., Göritz C., Covic M., Schäffner I., Schwarz T.J., Karaca E., Kempkes B., Kremmer E., Pfrieger F.W., Espinosa L., Bigas A., Giachino C., Taylor V., Frisén J., Lie C.D.
  
• Role of astroglial connexin30 in hippocampal gap junction coupling. Glia, Vol. 59. 2011, Issue 3, pp. 511–519.
  Gosejacob D., Dublin P., Bedner P., Huttmann K., Zhang J., Tress O., Willecke K., Pfrieger F., Steinhauser C., Theis M.
  
• Relevance of exocytotic glutamate release from retinal glia. Neuron, Vol. 74. 2012, Issue 3, pp. 504–516.
  Slezak M., Pfrieger F. W. et al.
  
• CXCR4 prevents dispersion of granule neuron precursors in the adult dentate gyrus. Hippocampus, Vol. 23. 2013, Issue 12, pp. 1345–1358.
  Schultheiß C., Abe P., Hoffmann F., Mueller W., Kreuder A.E., Schütz D., Haege S., Redecker C., Keiner S., Kannan S., Claasen J.H., Pfrieger F.W., Stumm R.
  
• Calcium dynamics in astrocyte processes during neurovascular coupling. Nature Neuroscience, Vol. 18. 2015, pp. 210–218.
  Otsu Y, Couchman K, Lyons DG, Collot M, Agarwal A, Mallet J, Pfrieger FW, Bergles DE, Charpak S