Generation and characterization of an Nse-CreERT2 transgenic line suitable for inducible gene manipulation in cerebellar granule cells.

Theresa Pohlkamp,Laura Steller,Hans H Bock,Joachim Herz,Thomas Günther,Petra May,Michael Frotscher,Roland Schüle,Branden Nelson

doi:10.1371/journal.pone.0100384

Abstract

We created an Nse-CreERT2 mouse line expressing the tamoxifen-inducible CreERT2 recombinase under the control of the neuron-specific enolase (Nse) promoter. By using Cre reporter lines we could show that this Nse-CreERT2 line has recombination activity in the granule cells of all cerebellar lobules as well as in postmitotic granule cell precursors in the external granular layer of the developing cerebellum. A few hippocampal dentate gyrus granule cells showed Cre-mediated recombination as well. Cre activity could be induced in both the developing and adult mouse brain. The established mouse line constitutes a valuable tool to study the function of genes expressed by cerebellar granule cells in the developing and adult brain. In combination with reporter lines it is a useful model to analyze the development and maintenance of the cerebellar architecture including granule cell distribution, migration, and the extension of granule cell fibers in vivo.

Highlights

The cerebellum plays an important role in motor control and is involved in cognitive processing and motor learning [1,2]
The small-sized granule cells (GC) in the cerebellum are the most abundant neurons in the mammalian brain. They are densely packed into a thick layer of the cerebellar cortex, the GC layer (GCL)
The results show that CreERT2-recombinase in this mouse line enables a tamoxifen-inducible recombination of LoxP-flanked genomic regions that is specific to the GC population in the cerebellum

Summary

Introduction

The cerebellum plays an important role in motor control and is involved in cognitive processing and motor learning [1,2]. The small-sized granule cells (GC) in the cerebellum are the most abundant neurons in the mammalian brain. They are densely packed into a thick layer of the cerebellar cortex, the GC layer (GCL). From there GCPs migrate tangentially to form the external granular layer (EGL), a secondary proliferative zone beneath the cerebellar pial surface [4,5,6,7]. Postmitotic GCPs in the deep EGL extend bipolar processes, which will become parallel fiber axons, and migrate tangentially – in parallel to the pial surface – before they turn orthogonally, to migrate radially along Bergmann glial fibers. After passing the ML and the Purkinje cell layer, GCs reach the deeper internal granular layer (IGL), which later becomes the mature

Methods

Results

Conclusion