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BMC Neuroscience

, 8:63

First Online: 02 August 2007Received: 10 April 2007Accepted: 02 August 2007


BackgroundThe analysis of the role of genes in important brain functions like learning, memory and synaptic plasticity requires gene inactivation at the adult stage to exclude developmental effects, adaptive changes or even lethality. In order to achieve temporally controlled somatic mutagenesis, the Cre-loxP-recombination system has been complemented with the tamoxifen-inducible fusion protein consisting of Cre recombinase and the mutated ligand binding domain of the human estrogen receptor CreER. To induce recombination of conditional alleles in neurons of the adult forebrain, we generated a bacterial artificial chromosome-derived transgene expressing the CreER fusion protein under control of the regulatory elements of the CaMKIIα gene CaMKCreER transgene.

ResultsWe established three mouse lines harboring one, two and four copies of the CaMKCreER transgene. The CaMKCreER transgene displayed reliable and copy number-dependent expression of Cre recombinase specifically in neurons of the adult forebrain. Using Cre reporter mice we show very low background activity of the transgene in absence of the ligand and efficient induction of recombination upon tamoxifen treatment in all three lines. In addition, we demonstrate in mice harboring two conditional glucocorticoid receptor GR alleles and the CaMKCreER transgene spatially restricted loss of GR protein expression in neurons of the adult forebrain upon tamoxifen treatment.

ConclusionThis is to our knowledge the first approach allowing highly efficient inducible gene inactivation in neurons of the adult mouse forebrain. This new approach will be a useful tool to dissect the function of specific genes in the adult forebrain. Effects of gene inactivation on pre- and postnatal brain development and compensatory mechanisms elicited by an early onset of gene inactivation can now be excluded.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-8-63 contains supplementary material, which is available to authorized users.

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Autor: Gitta Erdmann - Günther Schütz - Stefan Berger


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