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Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons.

DLX1 and DLX2 transcription factors are necessary for forebrain GABAergic neuron differentiation, migration, and survival. We generated transgenic mice that express Cre-recombinase under the control of two ultra-conserved DNA elements near the Dlx1 and 2 locus termed I12b and URE2. We show that Cre-recombinase is active in a "Dlx-pattern" in the embryonic forebrain of transgenic mice. I12b-Cre is more active than URE2-Cre in the medial ganglionic eminences and its derivatives. Fate-mapping of EGFP+ cells in adult Cre;Z/EG animals demonstrated that GABAergic neurons, but not glia, are labeled. Most NPY+, nNOS+, parvalbumin+, and somatostatin+ cells are marked by I12b-Cre in the cortex and hippocampus, while 25-40% of these interneuron subtypes are labeled by URE2-Cre. Labeling of neurons generated between E12.5 to E15.5 indicated differences in birth-dates of EGFP+ cells that populate the olfactory bulb, hippocampus, and cortex. Finally, we provide the first in vivo evidence that both I12b and URE2 are direct targets of DLX2 and require Dlx1 and Dlx2 expression for proper activity.

Pubmed ID: 19026749 RIS Download

Mesh terms: Animals | Animals, Newborn | Biomarkers | Cell Lineage | Enhancer Elements, Genetic | Female | Gene Expression Regulation, Developmental | Homeodomain Proteins | Integrases | Interneurons | Male | Mice | Mice, Transgenic | Neuroglia | Prosencephalon | Transcription Factors | Transgenes | gamma-Aminobutyric Acid

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Associated grants

  • Agency: NINDS NIH HHS, Id: K08 NS062744
  • Agency: NIMH NIH HHS, Id: R01 MH49428
  • Agency: NIMH NIH HHS, Id: K05 MH065670-05
  • Agency: NICHD NIH HHS, Id: HD-07162H
  • Agency: NIMH NIH HHS, Id: R01 MH081880
  • Agency: NIMH NIH HHS, Id: R01 MH049428-15
  • Agency: NIMH NIH HHS, Id: K05 MH065670
  • Agency: NICHD NIH HHS, Id: T32 HD007162
  • Agency: NIMH NIH HHS, Id: R37 MH049428
  • Agency: NIMH NIH HHS, Id: R01 MH049428

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