Visualizing corticotropin-releasing hormone receptor type 1 expression and neuronal connectivities in the mouse using a novel multifunctional allele

Autor: Claudia Kühne, Wolfgang Wurst, Jan M. Deussing, Jochen Graw, Martin Hrabě de Angelis, Günther Schütz, Oliver Puk
Rok vydání: 2012
Předmět:
Central Nervous System
Corticotropin-releasing hormone receptor
Striatum
Mtap2 protein
mouse
methods [Gene Knock-In Techniques]
cytology [Central Nervous System]
immunology [Tyrosine 3-Monooxygenase]
Mice
Antibody Specificity
immunology [Adrenocorticotropic Hormone]
cytology [Embryonic Stem Cells]
Neural Pathways
metabolism [Protein Kinase C]
Gene Knock-In Techniques
metabolism [Receptor
trkC]
Receptor
physiology [Viscera]
Protein Kinase C
Mice
Knockout
protein kinase C gamma
General Neuroscience
immunology [Protein Kinase C]
physiology [Central Nervous System]
Lac Operon
Models
Animal
GABAergic
cytology [Neural Pathways]
Microtubule-Associated Proteins
genetics [Receptors
Corticotropin-Releasing Hormone]
genetics [Mice
Knockout]
Tyrosine 3-Monooxygenase
Cre recombinase
physiology [Neural Pathways]
tau Proteins
Biology
immunology [Receptor
trkC]
metabolism [RNA
Messenger]
Receptors
Corticotropin-Releasing Hormone
metabolism [Adrenocorticotropic Hormone]
Glutamatergic
immunology [Receptors
Corticotropin-Releasing Hormone]
Adrenocorticotropic Hormone
Electroretinography
metabolism [Receptors
Corticotropin-Releasing Hormone]
Animals
Receptor
trkC
ddc:610
RNA
Messenger
Allele
Alleles
Embryonic Stem Cells
physiology [Axons]
Reporter gene
genetics [Lac Operon]
metabolism [Microtubule-Associated Proteins]
CRF receptor type 1
immunology [Microtubule-Associated Proteins]
Axons
physiology [Embryonic Stem Cells]
metabolism [Tyrosine 3-Monooxygenase]
genetics [tau Proteins]
Viscera
Neuroscience
Zdroj: The journal of comparative neurology 520(14), 3150-3180 (2012). doi:10.1002/cne.23082
ISSN: 1096-9861
DOI: 10.1002/cne.23082
Popis: The corticotropin-releasing hormone (CRH) and its type 1 receptor (CRHR1) play a central role in coordinating the endocrine, autonomic, and behavioral responses to stress. A prerequisite to functionally dissect the complexity of the CRH/CRHR1 system is to unravel the identity of CRHR1-expressing neurons and their connectivities. Therefore, we used a knockin approach to genetically label CRHR1-expressing cells with a tau-lacZ (tZ) reporter gene. The distribution of neurons expressing β-galactosidase in the brain and the relative intensity of labeling is in full accordance with previously described Crhr1 mRNA expression. Combining the microtubule-binding properties of TAU with the Cre-loxP system allowed to direct the β-galactosidase to proximal dendrites, and in particular to axons. Thereby, we were able to visualize projections of CRHR1 neurons such as glutamatergic and dopaminergic afferent connections of the striatum and GABAergic CRHR1-expressing neurons located within its patch compartment. In addition, the tZ reporter gene revealed novel details of CRHR1 expression in the spinal cord, skin, and eye. CRHR1 expression in the retina prompted the identification of a new physiological role of CRHR1 related to the visual system. Besides its reporter properties, this novel CRHR1 allele comprises the possibility to conditionally restore or delete CRHR1 via Flp and Cre recombinase, respectively. Finally, the allele is suitable for further manipulations of the CRHR1 locus by recombinase-mediated cassette exchange. Taken together, this novel mouse allele will significantly facilitate the neuroanatomical analysis of CRHR1 circuits and opens up new avenues to address CRHR1 function in more detail. J. Comp. Neurol., 520:3150–3180, 2012. © 2012 Wiley Periodicals, Inc.
Databáze: OpenAIRE
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