title: Distribution of corticotropin-releasing factor neurons in the mouse brain: a study using corticotropin-releasing factor-modified yellow fluorescent protein knock-in mouse.
abstract: We examined the morphological features of corticotropin-releasing factor (CRF) neurons in a mouse line in which modified yellow fluorescent protein (Venus) was expressed under the CRF promoter. We previously generated the CRF-Venus knock-in mouse, in which Venus is inserted into the CRF gene locus by homologous recombination. In the present study, the neomycin phosphotransferase gene (Neo), driven by the pgk-1 promoter, was deleted from the CRF-Venus mouse genome, and a CRF-Venus∆Neo mouse was generated. Venus expression is much more prominent in the CRF-Venus∆Neo mouse when compared to the CRF-Venus mouse. In addition, most Venus-expressing neurons co-express CRF mRNA. Venus-expressing neurons constitute a discrete population of neuroendocrine neurons in the paraventricular nucleus of the hypothalamus (PVH) that project to the median eminence. Venus-expressing neurons were also found in brain regions outside the neuroendocrine PVH, including the olfactory bulb, the piriform cortex (Pir), the extended amygdala, the hippocampus, the neocortices, Barrington's nucleus, the midbrain/pontine dorsal tegmentum, the periaqueductal gray, and the inferior olivary nucleus (IO). Venus-expressing perikarya co-expressing CRF mRNA could be observed clearly even in regions where CRF-immunoreactive perikarya could hardly be identified. We demonstrated that the CRF neurons contain glutamate in the Pir and IO, while they contain gamma-aminobutyric acid in the neocortex, the bed nucleus of the stria terminalis, the hippocampus, and the amygdala. A population of CRF neurons was demonstrated to be cholinergic in the midbrain tegmentum. The CRF-Venus∆Neo mouse may be useful for studying the structural and functional properties of CRF neurons in the mouse brain.
authors.affiliation: Laboratory of Information Biology, Graduate School of Information Sciences, Tohoku University, 6-3-09 Aramaki-aza, Aoba, Sendai, 980-8579, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Kono
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan.
authors.forename: Kohtarou
authors.initials: K
authors.lastname: Konno
authors.affiliation: Laboratory of Information Biology, Graduate School of Information Sciences, Tohoku University, 6-3-09 Aramaki-aza, Aoba, Sendai, 980-8579, Japan.
authors.forename: Ashraf Hossain
authors.initials: AH
authors.lastname: Talukder
authors.affiliation: Laboratory of Information Biology, Graduate School of Information Sciences, Tohoku University, 6-3-09 Aramaki-aza, Aoba, Sendai, 980-8579, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fuse
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.affiliation: Laboratory of Information Biology, Graduate School of Information Sciences, Tohoku University, 6-3-09 Aramaki-aza, Aoba, Sendai, 980-8579, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Pharmaceutical Information Science, Tokushima University, Tokushima, 770-8505, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Horio
authors.affiliation: Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo, 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Laboratory of Information Biology, Graduate School of Information Sciences, Tohoku University, 6-3-09 Aramaki-aza, Aoba, Sendai, 980-8579, Japan. itoik@m.tohoku.ac.jp.|Department of Neuroendocrinology, Graduate School of Medicine, Tohoku University, Sendai, 980-8579, Japan. itoik@m.tohoku.ac.jp.
authors.forename: Keiichi
authors.identifier: http://orcid.org/0000-0002-2860-416X
authors.initials: K
authors.lastname: Itoi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000032:analysis*; D055879:Gene Knock-In Techniques / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008164:Luminescent Proteins; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D012333:RNA, Messenger; C054562:yellow fluorescent protein, Bacteria; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003346:Corticotropin-Releasing Hormone
keywords: Glucocorticoids; Homologous recombination; Immunofluorescence; In situ hybridization; Stress