Overexpression of vasopressin in the rat transgenic for the metallothionein-vasopressin fusion gene

Nagasaki, Hiroshi; Yokoi, Hisashi; Arima, Hiroshi; Hirabayashi, Masumi; Ishizaki, Seiji; Tachikawa, Kazushige; Murase, Takashi; Miura, Yoshitaka; Oiso, Yutaka

doi:10.1677/joe.0.1730035

Cited by 11 publications

(5 citation statements)

References 37 publications

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“…Details of the preparation of the rat transgenic for the human AVP gene used in this study have been previously reported (15). Rats were maintained under controlled conditions (23.0°C; lights on from 0900 to 2100), and all procedures were performed in accordance with institutional guidelines for animal care at Nagoya University School of Medicine, which conform to the National Institutes of Health animal care guidelines.…”

Section: Animalsmentioning

confidence: 99%

“…Recently, we (15,25) developed rats transgenic for the fusion gene consisting of the heavy metal-inducible promoter region of the mouse metallothionein I gene and human AVP gene (Tg). Interestingly, the change in water and electrolyte balance was relatively mild despite a markedly elevated plasma AVP level, suggesting that there may be adaptive mechanisms for maintaining water and electrolyte homeostasis against chronic AVP oversecretion from the earliest stage of life.…”

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confidence: 99%

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Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat

Tachikawa¹,

Yokoi²,

Nagasaki³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Although arginine vasopressin (AVP), an antidiuretic hormone, has been widely acknowledged to play an important role in cardiovascular regulation via V1a receptors (V1aR), its precise significance remains unclear. In this study, we investigated the effects of long-standing high plasma AVP status on cardiovascular regulation in the AVP-overexpressing transgenic (Tg) rat. Adult male homozygous Tg rats were compared with age-matched normal Sprague-Dawley rats as controls. There were no significant differences in mean arterial blood pressure (BP; MABP) or heart rate between Tg and control rats in the basal state. Subcutaneous injection of AVP significantly increased MABP in controls but did not cause any apparent increase in MABP in Tg rats. BP recovery from hemorrhage-induced hypotension was significantly delayed in Tg compared with control rats. Pretreatment with a selective V1aR antagonist, OPC-21268, which is thought to restore the downregulation of V1aR, markedly improved both of these impaired responses. Northern blot analysis confirmed that decreased expression of V1aR mRNA and pretreatment with V1aR antagonist significantly restored the downregulation of V1aR mRNA. These results suggest that the Tg rat has decreased sensitivity to the hypertensive effect of AVP due to downregulation of V1aR, which may function as an adaptive mechanism to maintain normal BP against chronic hypervasopressinemia. In addition, impaired restoration of BP after hemorrhage-induced hypotension in Tg rats supports a physiological role of AVP in cardiovascular regulation.

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Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat

Tachikawa¹,

Yokoi²,

Nagasaki³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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“…Details of the preparation of the rat transgenic for the human AVP gene used in this study have been described (Nagasaki et al 2002). Rats were maintained under controlled conditions (23 C; lights on 0900-2100 h), and all procedures were performed in accordance with the institutional guidelines for animal care at Nagoya University School of Medicine, which conform with the NIH animal care guidelines.…”

Section: Animalsmentioning

confidence: 99%

“…Recently, we have generated a rat transgenic for the fusion gene consisting of the heavy metal-inducible promoter region of the mouse metallothionein I gene and human AVP gene (Nagasaki et al 2002). We have revealed that in the rat (1) plasma AVP immunoreactivity was remarkably elevated and increased further by administering zinc sulfate, (2) AVP protein was processed correctly and revealed almost equivalent bioactivity with authentic AVP, and (3) the plasma [Na + ] concentration was not different from control rats under basal conditions, while it declined compared with control rats when a liquid diet containing zinc was provided.…”

Section: Introductionmentioning

confidence: 99%

Adaptation to sustained high plasma vasopressin in water and electrolyte homeostasis in the rat transgenic for the metallothionein-vasopressin fusion gene

Yokoi

Nagasaki

Tachikawa

et al. 2002

Journal of Endocrinology

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Prolonged exposure of tissues to a receptor agonist often leads to adaptive changes that limit the subsequent responsiveness of the tissue to the same agonist. Recently, we have generated rats transgenic for the metallothionein I-human arginine vasopressin (AVP) fusion gene (Tg), which produced high plasma AVP with relatively preserved renal water excretion, suggesting that there might be adaptive mechanism(s) for maintaining water and electrolyte homeostasis against chronic AVP oversecretion from the earliest stage of life. In this study, to investigate whether down-regulation of AVP V2 receptor (V2R), which could possibly be caused by long-standing high plasma AVP, participates in this adaptive mechanism(s), non-peptidic V2R antagonist OPC31260 was administered to reverse the down-regulation, and water loading was performed after V2R antagonist treatment had been withdrawn. Additionally, to confirm the down-regulation, Northern blotting analysis for V2R mRNA was carried out. Tg rats showed slightly decreased urine volume and water intake with an equivalent plasma [Na + ] level (Tg 140·4 0·6 mEq/l; control 139·3 0·6 mEq/l) under basal conditions. After water loading using a liquid diet containing zinc, which stimulates the promoter region in the transgene, the urine increase showed only limited suppression with a dramatically increased plasma AVP level and mild hyponatremia (135·8 1·8 mEq/l) in Tg rats. When diet containing OPC31260 had been provided for 4 days until the day before the start of water loading, antidiuresis and hyponatremia (125·4 1·4 mEq/l) were significantly potentiated. V2R mRNA expression in kidney was significantly less in Tg rats than in control rats under basal conditions, and this suppression was restored by OPC31260 treatment to levels comparable with those of control rats. These results suggest that long-standing high plasma AVP causes V2R down-regulation, and it may play an important role in the adaptive mechanism(s) for maintaining water and electrolyte homeostasis in chronically AVP-overexpressing rats.

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“…M Molecular weight marker (UX174 Hae III digest), P positive control sample for each transgene Transgenic Res (2009) 18:135-141 139 heavy metals (Zn 2? ) to Tg rats to emphasize the MT promoter (Nagasaki et al 2002). Further research is necessary that considers the correlation between the expression of the c-myc gene and the conditioning of the seminiferous tubules for spermatogonial transplantation in the rats.…”

Section: Resultsmentioning

confidence: 99%

Availability of subfertile transgenic rats expressing the c-myc gene as recipients for spermatogonial transplantation

et al. 2008

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The spermatogonial transplantation system was applied to evaluate stem cell kinetics and niche quality and to produce gene-modified animals using the stem cells after homologous recombination-based selection. This study was designed to determine whether the transplanted spermatogonia were able to proliferate and differentiate in male rats expressing the c-myc transgene under control of the human metallothionein IIA promoter (MT-myc Tg rats). Donor testicular cells were prepared from heterozygous chicken beta actin (CAG)/enhanced green fluorescent protein (EGFP)-transgenic rats (EGFP Tg rats) during the second week after birth and injected into the seminiferous tubules of the MT-myc Tg rats (line-A and -B; both subfertile) or rats pretreated with busulfan to remove endogenous spermatogonia. Three to four months after transplantation, cell colonies with EGFP fluorescence were detected in 36% (4/11), 40% (8/20), and 71% (5/7) of the transplanted testes in line-A MT-myc Tg rats, line-B MT-myc Tg rats, and busulfan-treated rats, respectively. No EGFP-positive colonies were detected when wild-type male rats were used as recipients (0/7; testis-basis). The histopathological and immunofluorescent examination of the serial sections from the transplanted testes showed normal spermatogenesis of the donor spermatogonia, but atrophy of the recipient seminiferous tubules. Microinsemination with round spermatids and mature spermatozoa derived from EGFP-positive testes in line-A rats resulted 26% (10/39 transferred) and 23% (11/48 transferred) full-term offspring, respectively. Thus, the MT-myc Tg male rats were suitable as potent recipients for spermatogonial transplantation without any chemical pretreatment to remove the endogenous spermatogonia.

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Overexpression of vasopressin in the rat transgenic for the metallothionein-vasopressin fusion gene

Cited by 11 publications

References 37 publications

Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat

Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat

Adaptation to sustained high plasma vasopressin in water and electrolyte homeostasis in the rat transgenic for the metallothionein-vasopressin fusion gene

Availability of subfertile transgenic rats expressing the c-myc gene as recipients for spermatogonial transplantation

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