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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Autores principales: Noaín, D., Avale, M.E., Wedemeyer, C., Calvo, D., Peper, M., Rubinstein, M.
Formato: JOUR
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Acceso en línea:http://hdl.handle.net/20.500.12110/paper_0953816X_v24_n9_p2429_Noain
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spelling todo:paper_0953816X_v24_n9_p2429_Noain2023-10-03T15:51:17Z Identification of brain neurons expressing the dopamine D4 receptor gene using BAC transgenic mice Noaín, D. Avale, M.E. Wedemeyer, C. Calvo, D. Peper, M. Rubinstein, M. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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, D.
Avale, M.E.
Wedemeyer, C.
Calvo, D.
Peper, M.
Rubinstein, M.
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).
format JOUR
author Noaín, D.
Avale, M.E.
Wedemeyer, C.
Calvo, D.
Peper, M.
Rubinstein, M.
author_facet Noaín, D.
Avale, M.E.
Wedemeyer, C.
Calvo, D.
Peper, M.
Rubinstein, M.
author_sort Noaín, D.
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
url http://hdl.handle.net/20.500.12110/paper_0953816X_v24_n9_p2429_Noain
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