The mineralocorticoid receptor knockout in medaka is further validated by glucocorticoid receptor compensation

Sakamoto, Tatsuya; Yoshiki, Madoka; Sakamoto, Hirotaka

doi:10.1038/sdata.2017.189

Cited by 9 publications

(7 citation statements)

References 20 publications

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“…To compensate for the loss of mr, medaka mr KO results in an increase of gr1 expression (one of the two paralogue gr genes present in this teleost species) in brain and eyes but not in the osmoregulatory organs (Sakamoto et al 2017), confirming the lack of Mr activities in ion balance physiology. In zebrafish, compensation between CRs can be detected in the gr ia30 mutant line that shows a four-times increase of mr expression in 5-dpf larvae.…”

Section: Mutants Of Glucocorticoid Receptors In Zebrafishmentioning

confidence: 72%

Glucocorticoid receptor activities in the zebrafish model: a review

Dinarello

Licciardello

Fontana

et al. 2020

Journal of Endocrinology

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Glucocorticoids (GCs) are steroid hormones that contribute to the regulation of many physiological processes, such as inflammation, metabolism and stress response, mainly through binding to their cognate receptor, GR, which works as a ligand-activated transcription factor. Due to their pleiotropy and the common medical use of these steroids to treat patients affected by different pathologies, the investigation of their mechanisms of action is extremely important in biology and clinical research. The evolutionary conservation of GCs’ physiological functions, biosynthesis pathways as well as sequence and structure of their nuclear receptor, in the last 20 years has stimulated the use of zebrafish (a teleost of Ciprinidae family) as a reliable model organism to investigate the topic. In this review, we wanted to collect many of the most important discoveries that the scientific community has obtained using zebrafish to study GCs and their receptors. The paper begins by describing the experiments with transient knockdown of zebrafish gr to gain information mainly during development and continues with the discoveries provided by the generation of transgenic reporter lines. Finally, we discuss how the generation of mutant lines for either gr or the enzymes involved in GCs’ synthesis has significantly advanced our knowledge on GCs’ biology.

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Section: Mutants Of Glucocorticoid Receptors In Zebrafishmentioning

confidence: 72%

Glucocorticoid receptor activities in the zebrafish model: a review

Dinarello

Licciardello

Fontana

et al. 2020

Journal of Endocrinology

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“…Medaka with MR have induced GR expression in the eyes and brain, but not in osmoregulatory organs [14]. This shows that glucocorticoid signaling, and not mineralocorticoid signaling, is important in body fluid regulation of the fish [13,39].…”

Section: A Conserved Principal Function Of Corticosteroid Signalinmentioning

confidence: 99%

‘Central’ Actions of Corticosteroid Signaling Suggested by Constitutive Knockout of Corticosteroid Receptors in Small Fish

Sakamoto

2019

Nutrients

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This review highlights recent studies of the functional implications of corticosteroids in some important behaviors of model fish, which are also relevant to human nutrition homeostasis. The primary actions of corticosteroids are mediated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which are transcription factors. Zebrafish and medaka models of GR- and MR-knockout are the first constitutive corticosteroid receptor-knockout animals that are viable in adulthood. Similar receptor knockouts in mice are lethal. In this review, we describe the physiological and behavioral changes following disruption of the corticosteroid receptors in these models. The GR null model has peripheral changes in nutrition metabolism that do not occur in a mutant harboring a point mutation in the GR DNA-binding domain. This suggests that these are not “intrinsic” activities of GR. On the other hand, we propose that integration of visual responses and brain behavior by corticosteroid receptors is a possible “intrinsic”/principal function potentially conserved in vertebrates.

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“…GR protein levels are known to autoregulate gr mRNA, increasing transcript abundance when GR protein is occupied, and available receptor levels decrease in fish tissues (Sathiyaa and Vijayan, 2003;Vijayan et al, 2003). Additionally, mr-knockout (KO) in medaka has been reported to increase GR levels to compensate for the absence of the MR (Sakamoto et al, 2017). Similarly, it seems from the current study that if the levels of MR are altered in the absence of added cortisol, the model gill epithelium of rainbow trout can increase the abundance of gr2, possibly to compensate by enabling a full-fledged response to cortisol once the ligand is present.…”

Section: Mr Is Expressed In Model Gill Epithelium Cells and Is Important For Normal Barrier Functionmentioning

confidence: 99%

The mineralocorticoid receptor contributes to barrier function of a model fish gill epithelium

Kolosov

Kelly

2019

Journal of Experimental Biology

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Cortisol-induced epithelial tightening of a primary cultured rainbow trout gill epithelium model occurs in association with reduced paracellular permeability and increased abundance of select barrier-forming TJ proteins. Corticosteroid receptor (CR) pharmacological blocker studies have suggested that to produce this tightening effect, cortisol acts on the mineralocorticoid receptor (MR) as well as glucocorticoid receptors (GRs). This study considered how cortisol influenced model gill epithelium permeability and TJ properties by transcriptional knockdown of the gene encoding MR (mr-KD) using double-stranded RNA. Following mr-KD a significant reduction in MR protein abundance was observed in the epithelium. The mr-KD epithelium demonstrated reduced transepithelial resistance (TER) and increased the paracellular flux of [3H] polyethylene glycol (MW 400 kDa, PEG-400). Concurrently, mRNA abundance of gr2 and 11βhsd increased, indicating a possible compensatory response to mr-KD. Transcript abundance of claudin (cldn) -6, -8d, 23a and -28b decreased while cldn-20a increased in mr-KD preparations. Cortisol-induced epithelial tightening was enhanced in mr-KD preparations, suggesting that alterations in CRs and TJ composition augmented model epithelium barrier function in response to lowered MR abundance. Cortisol treatment significantly increased the transcript and protein abundance of TJ proteins such as cldn/Cldn -8d, and -28b. However, in mr-KD preparations, Cldn-28b protein abundance did not significantly alter in response to cortisol treatment, while Cldn-8d significantly elevated. Data suggest that mr-KD compromises normal barrier function of a primary cultured rainbow trout gill epithelium both in the presence and absence of cortisol and that Cldn-28b protein abundance may be modulated by cortisol via the MR only.

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The mineralocorticoid receptor knockout in medaka is further validated by glucocorticoid receptor compensation

Cited by 9 publications

References 20 publications

Glucocorticoid receptor activities in the zebrafish model: a review

Glucocorticoid receptor activities in the zebrafish model: a review

‘Central’ Actions of Corticosteroid Signaling Suggested by Constitutive Knockout of Corticosteroid Receptors in Small Fish

The mineralocorticoid receptor contributes to barrier function of a model fish gill epithelium

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