title: Principal function of mineralocorticoid signaling suggested by constitutive knockout of the mineralocorticoid receptor in medaka fish.
abstract: As in osmoregulation, mineralocorticoid signaling is implicated in the control of brain-behavior actions. Nevertheless, the understanding of this role is limited, partly due to the mortality of mineralocorticoid receptor (MR)-knockout (KO) mice due to impaired Na+reabsorption. In teleost fish, a distinct mineralocorticoid system has only been identified recently. Here, we generated a constitutive MR-KO medaka as the first adult-viable MR-KO animal, since MR expression is modest in osmoregulatory organs but high in the brain of adult medaka as for most teleosts. Hyper- and hypo-osmoregulation were normal in MR-KO medaka. When we studied the behavioral phenotypes based on the central MR localization, however, MR-KO medaka failed to track moving dots despite having an increase in acceleration of swimming. These findings reinforce previous results showing a minor role for mineralocorticoid signaling in fish osmoregulation, and provide the first convincing evidence that MR is required for normal locomotor activity in response to visual motion stimuli, but not for the recognition of these stimuli per se. We suggest that MR potentially integrates brain-behavioral and visual responses, which might be a conserved function of mineralocorticoid signaling through vertebrates. Importantly, this fish model allows for the possible identification of novel aspects of mineralocorticoid signaling.
authors.affiliation: Ushimado Marine Institute, Faculty of Science, Okayama University, Setouchi, 701-4303, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: Ushimado Marine Institute, Faculty of Science, Okayama University, Setouchi, 701-4303, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Yoshiki
authors.affiliation: Ushimado Marine Institute, Faculty of Science, Okayama University, Setouchi, 701-4303, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Laboratory of Fish Physiology, Graduate School of Biosphere Science, Hiroshima University, Higashihiroshima, 739-8528, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 819-0395, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ogino
authors.affiliation: Department of Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, 526-0829, Japan.
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Ikeuchi
authors.affiliation: Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, Toyama, 930-8555, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nakamachi
authors.affiliation: Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, Toyama, 930-8555, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Konno
authors.affiliation: Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, Toyama, 930-8555, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Ushimado Marine Institute, Faculty of Science, Okayama University, Setouchi, 701-4303, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sakamoto
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000502:physiology*; D005123:Eye / Q000378:metabolism*; D008124:Locomotion; D008901:Mineralocorticoids / Q000378:metabolism*; D009990:Oryzias / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D064587:Osmoregulation / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D014796:Visual Perception / Q000502:physiology*
chemical_list: D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid