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Off-Target Effects in Transgenic Mice: Characterization of Dopamine Transporter (DAT)-Cre Transgenic Mouse Lines Exposes Multiple Non-Dopaminergic Neuronal Clusters Available for Selective Targeting within Limbic Neurocircuitry
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
Oramacell, F-75006 Paris, France.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
Karolinska Inst, Dept Neurosci, Biomed C4, S-17165 Solna, Sweden.
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2019 (English)In: ENEURO, ISSN 2373-2822, Vol. 6, no 5, article id ENEURO.0198-19.2019Article in journal (Refereed) Published
Abstract [en]

Transgenic mouse lines are instrumental in our attempt to understand brain function. Promoters driving transgenic expression of the gene encoding Cre recombinase are crucial to ensure selectivity in Cre-mediated targeting of floxed alleles using the Cre-Lox system. For the study of dopamine (DA) neurons, promoter sequences driving expression of the Dopamine transporter (Dat) gene are often implemented and several DAT-Cre transgenic mouse lines have been found to faithfully direct Cre activity to DA neurons. While evaluating an established DAT-Cre mouse line, reporter gene expression was unexpectedly identified in cell somas within the amygdala. To indiscriminately explore Cre activity in DAT-Cre transgenic lines, systematic whole-brain analysis of two DAT-Cre mouse lines was performed upon recombination with different types of floxed reporter alleles. Results were compared with data available from the Allen Institute for Brain Science. The results identified restricted DAT-Cre-driven reporter gene expression in cell clusters within several limbic areas, including amygdaloid and mammillary subnuclei, septum and habenula, areas classically associated with glutamatergic and GABAergic neurotransmission. While no Dat gene expression was detected, ample co-localization between DAT-Cre-driven reporter and markers for glutamatergic and GABAergic neurons was found. Upon viral injection of a fluorescent reporter into the amygdala and habenula, distinct projections from non-dopaminergic DAT-Cre neurons could be distinguished. The study demonstrates that DAT-Cre transgenic mice, beyond their usefulness in recombination of floxed alleles in DA neurons, could be implemented as tools to achieve selective targeting in restricted excitatory and inhibitory neuronal populations within the limbic neurocircuitry.

Place, publisher, year, edition, pages
2019. Vol. 6, no 5, article id ENEURO.0198-19.2019
Keywords [en]
amygdala, Gad1, habenula, mammillary, septum, Vglut2
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-397678DOI: 10.1523/ENEURO.0198-19.2019ISI: 000494278900027PubMedID: 31481399OAI: oai:DiVA.org:uu-397678DiVA, id: diva2:1373929
Funder
Swedish Research Council, 2017-02039Swedish Research Council, 2014-3804Swedish Research Council, 2013-4657Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved

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