title: Visualizing corticotropin-releasing hormone receptor type 1 expression and neuronal connectivities in the mouse using a novel multifunctional allele.
abstract: 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.
authors.affiliation: Max Planck Institute of Psychiatry, 80804 Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kühne
authors.forename: Oliver
authors.initials: O
authors.lastname: Puk
authors.forename: Jochen
authors.initials: J
authors.lastname: Graw
authors.forename: Martin
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Jan M
authors.initials: JM
authors.lastname: Deussing
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000276:immunology / Q000378:metabolism; D000483:Alleles; D000818:Animals; D000918:Antibody Specificity; D001369:Axons / Q000502:physiology; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D004596:Electroretinography; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D055879:Gene Knock-In Techniques / Q000379:methods*; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000276:immunology / Q000378:metabolism; D023421:Models, Animal; D009434:Neural Pathways / Q000166:cytology / Q000502:physiology*; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020812:Receptor, trkC / Q000276:immunology / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000276:immunology / Q000378:metabolism; D014781:Viscera / Q000502:physiology; D016875:tau Proteins / Q000235:genetics; D000099052:CRF Receptor, Type 1
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D016875:tau Proteins; D000099052:CRF Receptor, Type 1; D000324:Adrenocorticotropic Hormone; D014446:Tyrosine 3-Monooxygenase; C087857:protein kinase C gamma; D020812:Receptor, trkC; D011493:Protein Kinase C