Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice
The dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the extremely polymorphic nature of the human gene and the genetic association with attention deficit and hyperactivity disorder (ADHD). Several efforts have been undertaken...
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2006
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paper:paper_0953816X_v24_n9_p2429_Noain2023-06-08T15:55:29Z Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice Noaín, Daniela María Clara Avale, María Elena Wedemeyer, Carolina Calvo, Daniel Juan Peper, Marcela Rubinstein, Marcelo Anterior olfactory nucleus Green fluorescent protein Lateral parabrachial nucleus Prefrontal cortex Ventral pallidum dopamine 4 receptor enhanced green fluorescent protein animal cell animal experiment animal tissue article bacterial artificial chromosome brain nerve cell cell labeling cingulate gyrus corpus striatum dopaminergic transmission female gene expression profiling gene identification globus pallidus hippocampus immunohistochemistry limbic cortex male mesencephalon mouse nonhuman olfactory nucleus orbital cortex parabrachial nucleus prefrontal cortex priority journal receptor gene transgenic mouse Animals Brain Chromosomes, Artificial, Bacterial Embryo Green Fluorescent Proteins Immunohistochemistry Male Mice Mice, Transgenic Microscopy, Confocal Neurons Patch-Clamp Techniques Receptors, Dopamine D4 The dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the extremely polymorphic nature of the human gene and the genetic association with attention deficit and hyperactivity disorder (ADHD). Several efforts have been undertaken to determine the D4R expression pattern in the brain using immunohistochemistry, binding autoradiography and in situ hybridization, but the overall published results present large discrepancies. Here, we have explored an alternative genetic approach by studying bacterial artificial chromosome (BAC) transgenic mice that express enhanced green fluorescent protein (EGFP) under the transcriptional control of the mouse dopamine D4 receptor gene (Drd4). Immunohistochemical analysis performed in brain sections of Drd4-EGFP transgenic mice using an anti-EGFP polyclonal antibody showed that transgenic expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral agranular portions. In addition, discrete groups of Drd4-EGFP labelled neurons were observed in the anterior olfactory nucleus, ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD. © The Authors (2006). Fil:Noaín, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Avale, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wedemeyer, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Calvo, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Peper, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0953816X_v24_n9_p2429_Noain http://hdl.handle.net/20.500.12110/paper_0953816X_v24_n9_p2429_Noain |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Anterior olfactory nucleus Green fluorescent protein Lateral parabrachial nucleus Prefrontal cortex Ventral pallidum dopamine 4 receptor enhanced green fluorescent protein animal cell animal experiment animal tissue article bacterial artificial chromosome brain nerve cell cell labeling cingulate gyrus corpus striatum dopaminergic transmission female gene expression profiling gene identification globus pallidus hippocampus immunohistochemistry limbic cortex male mesencephalon mouse nonhuman olfactory nucleus orbital cortex parabrachial nucleus prefrontal cortex priority journal receptor gene transgenic mouse Animals Brain Chromosomes, Artificial, Bacterial Embryo Green Fluorescent Proteins Immunohistochemistry Male Mice Mice, Transgenic Microscopy, Confocal Neurons Patch-Clamp Techniques Receptors, Dopamine D4 |
spellingShingle |
Anterior olfactory nucleus Green fluorescent protein Lateral parabrachial nucleus Prefrontal cortex Ventral pallidum dopamine 4 receptor enhanced green fluorescent protein animal cell animal experiment animal tissue article bacterial artificial chromosome brain nerve cell cell labeling cingulate gyrus corpus striatum dopaminergic transmission female gene expression profiling gene identification globus pallidus hippocampus immunohistochemistry limbic cortex male mesencephalon mouse nonhuman olfactory nucleus orbital cortex parabrachial nucleus prefrontal cortex priority journal receptor gene transgenic mouse Animals Brain Chromosomes, Artificial, Bacterial Embryo Green Fluorescent Proteins Immunohistochemistry Male Mice Mice, Transgenic Microscopy, Confocal Neurons Patch-Clamp Techniques Receptors, Dopamine D4 Noaín, Daniela María Clara Avale, María Elena Wedemeyer, Carolina Calvo, Daniel Juan Peper, Marcela Rubinstein, Marcelo Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice |
topic_facet |
Anterior olfactory nucleus Green fluorescent protein Lateral parabrachial nucleus Prefrontal cortex Ventral pallidum dopamine 4 receptor enhanced green fluorescent protein animal cell animal experiment animal tissue article bacterial artificial chromosome brain nerve cell cell labeling cingulate gyrus corpus striatum dopaminergic transmission female gene expression profiling gene identification globus pallidus hippocampus immunohistochemistry limbic cortex male mesencephalon mouse nonhuman olfactory nucleus orbital cortex parabrachial nucleus prefrontal cortex priority journal receptor gene transgenic mouse Animals Brain Chromosomes, Artificial, Bacterial Embryo Green Fluorescent Proteins Immunohistochemistry Male Mice Mice, Transgenic Microscopy, Confocal Neurons Patch-Clamp Techniques Receptors, Dopamine D4 |
description |
The dopamine D4 receptor (D4R) has received considerable interest because of its higher affinity for atypical antipsychotics, the extremely polymorphic nature of the human gene and the genetic association with attention deficit and hyperactivity disorder (ADHD). Several efforts have been undertaken to determine the D4R expression pattern in the brain using immunohistochemistry, binding autoradiography and in situ hybridization, but the overall published results present large discrepancies. Here, we have explored an alternative genetic approach by studying bacterial artificial chromosome (BAC) transgenic mice that express enhanced green fluorescent protein (EGFP) under the transcriptional control of the mouse dopamine D4 receptor gene (Drd4). Immunohistochemical analysis performed in brain sections of Drd4-EGFP transgenic mice using an anti-EGFP polyclonal antibody showed that transgenic expression was predominant in deep layer neurons of the prefrontal cortex, particularly in the orbital, prelimbic, cingulate and rostral agranular portions. In addition, discrete groups of Drd4-EGFP labelled neurons were observed in the anterior olfactory nucleus, ventral pallidum, and lateral parabrachial nucleus. EGFP was not detected in the striatum, hippocampus or midbrain as described using other techniques. Given the fine specificity of EGFP expression in BAC transgenic mice and the high sensitivity of the EGFP antibody used in this study, our results indicate that Drd4 expression in the adult mouse brain is limited to a more restricted number of areas than previously reported. Its leading expression in the prefrontal cortex supports the importance of the D4R in complex behaviours depending on cortical dopamine (DA) transmission and its possible role in the etiopathophysiology of ADHD. © The Authors (2006). |
author |
Noaín, Daniela María Clara Avale, María Elena Wedemeyer, Carolina Calvo, Daniel Juan Peper, Marcela Rubinstein, Marcelo |
author_facet |
Noaín, Daniela María Clara Avale, María Elena Wedemeyer, Carolina Calvo, Daniel Juan Peper, Marcela Rubinstein, Marcelo |
author_sort |
Noaín, Daniela María Clara |
title |
Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice |
title_short |
Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice |
title_full |
Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice |
title_fullStr |
Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice |
title_full_unstemmed |
Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice |
title_sort |
identification of brain neurons expressing the dopamine d4 receptor gene using bac transgenic mice |
publishDate |
2006 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0953816X_v24_n9_p2429_Noain http://hdl.handle.net/20.500.12110/paper_0953816X_v24_n9_p2429_Noain |
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