Specific expression of an oxytocin-enhanced cyan fluorescent protein fusion transgene in the rat hypothalamus and posterior pituitary.

We have generated rats bearing an oxytocin (OXT)-enhanced cyan fluorescent protein (eCFP) fusion transgene designed from a murine construct previously shown to be faithfully expressed in transgenic mice. In situ hybridisation histochemistry revealed that the Oxt-eCfp fusion gene was expressed in the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) in these rats. The fluorescence emanating from eCFP was observed only in the SON, the PVN, the internal layer of the median eminence and the posterior pituitary (PP). In in vitro preparations, freshly dissociated cells from the SON and axon terminals showed clear eCFP fluorescence. Immunohistochemistry for OXT and arginine vasopressin (AVP) revealed that the eCFP fluorescence co-localises with OXT immunofluorescence, but not with AVP immunofluorescence in the SON and the PVN. Although the expression levels of the Oxt-eCfp fusion gene in the SON and the PVN showed a wide range of variations in transgenic rats, eCFP fluorescence was markedly increased in the SON and the PVN, but decreased in the PP after chronic salt loading. The expression of the Oxt gene was significantly increased in the SON and the PVN after chronic salt loading in both non-transgenic and transgenic rats. Compared with wild-type animals, euhydrated and salt-loaded male and female transgenic rats showed no significant differences in plasma osmolality, sodium concentration and OXT and AVP levels, suggesting that the fusion gene expression did not disturb any physiological processes. These results suggest that our new transgenic rats are a valuable new tool to identify OXT-producing neurones and their terminals.

[1]  Y. Ueta,et al.  Brain-derived neurotrophic factor inhibits spontaneous inhibitory postsynaptic currents in the rat supraoptic nucleus , 2009, Brain Research.

[2]  Y. Ueta,et al.  Response of Arginine Vasopressin‐Enhanced Green Fluorescent Protein Fusion Gene in the Hypothalamus of Adjuvant‐Induced Arthritic Rats , 2009, Journal of neuroendocrinology.

[3]  T. Serikawa,et al.  Rat resources in biomedical research. , 2009, Current pharmaceutical biotechnology.

[4]  C. Viero,et al.  The role of calcium in the action and release of vasopressin and oxytocin from CNS neurones/terminals to the heart. , 2008, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[5]  H. Fujihara,et al.  Specific Expression of Optically Active Reporter Gene in Arginine Vasopressin‐Secreting Neurosecretory Cells in the Hypothalamic‐Neurohypophyseal System , 2008, Journal of neuroendocrinology.

[6]  H. Gainer,et al.  Differential Kinetics of Oxytocin and Vasopressin Heteronuclear RNA Expression in the Rat Supraoptic Nucleus in Response to Chronic Salt Loading In vivo , 2007, Journal of neuroendocrinology.

[7]  Y. Ueta,et al.  Physiological Studies of Stress Responses in the Hypothalamus of Vasopressin‐Enhanced Green Fluorescent Protein Transgenic Rat , 2007, Journal of neuroendocrinology.

[8]  H. Morita,et al.  Exaggerated Response of Arginine Vasopressin‐Enhanced Green Fluorescent Protein Fusion Gene to Salt Loading without Disturbance of Body Fluid Homeostasis in Rats , 2006, Journal of neuroendocrinology.

[9]  Alison Abbott,et al.  Laboratory animals: The Renaissance rat , 2004, Nature.

[10]  Kumiko Ui-Tei,et al.  Characterization of voltage-gated calcium currents in gonadotropin-releasing hormone neurons tagged with green fluorescent protein in rats. , 2003, Endocrinology.

[11]  H. Gainer,et al.  Transgenesis and the Study of Expression, Cellular Targeting and Function of Oxytocin, Vasopressin and Their Receptors , 2003, Neuroendocrinology.

[12]  G. Leng,et al.  Neurosteroid regulation of oxytocin and vasopressin release from the rat supraoptic nucleus , 2003, The Journal of physiology.

[13]  D. Murphy,et al.  In Vivo Gene Transfer Studies on the Regulation and Function of the Vasopressin and Oxytocin Genes , 2003, Journal of neuroendocrinology.

[14]  Gareth Leng,et al.  Intracellular calcium stores regulate activity-dependent neuropeptide release from dendrites , 2002, Nature.

[15]  H. Gainer,et al.  Targeting of green fluorescent protein to secretory granules in oxytocin magnocellular neurons and its secretion from neurohypophysial nerve terminals in transgenic mice. , 2002, Endocrinology.

[16]  H. Gainer,et al.  Gene regulation in the magnocellular hypothalamo-neurohypophysial system. , 2001, Physiological reviews.

[17]  G. Dayanithi,et al.  Intracellular calcium signalling in magnocellular neurones of the rat supraoptic nucleus: understanding the autoregulatory mechanisms , 2000, Experimental physiology.

[18]  Ginns,et al.  Transgenic Expression of Green Fluorescent Protein in Mouse Oxytocin Neurones , 1999, Journal of neuroendocrinology.

[19]  G. Wang,et al.  An R-Type Ca2+ Current in Neurohypophysial Terminals Preferentially Regulates Oxytocin Secretion , 1999, The Journal of Neuroscience.

[20]  Daniel F. Hanley,et al.  GABA- and Glutamate-Activated Channels in Green Fluorescent Protein-Tagged Gonadotropin-Releasing Hormone Neurons in Transgenic Mice , 1999, The Journal of Neuroscience.

[21]  David Carment,et al.  Three's Company , 1998 .

[22]  S. Lightman,et al.  Hypothalamic nitric oxide synthase gene expression is regulated by thyroid hormones. , 1995, Endocrinology.

[23]  P. Emson,et al.  Evidence for the Co‐Expression of Oxytocin and Vasopressin Messenger Ribonucleic Acids in Magnocellular Neurosecretory Cells: Simultaneous Demonstration of Two Neurohypophysin Messenger Ribonucleic Acids by Hybridization Histochemistry , 1990, Journal of neuroendocrinology.

[24]  E. Mohr,et al.  Expression of the vasopressin and oxytocin genes in rats occurs in mutually exclusive sets of hypothalamic neurons , 1988, FEBS letters.

[25]  G. Dayanithi,et al.  Release of neuropeptides does not only occur at nerve terminals , 1988, Bioscience reports.

[26]  G. Dayanithi,et al.  Hormone release from isolated nerve endings of the rat neurohypophysis. , 1987, The Journal of physiology.

[27]  G. Dayanithi,et al.  The role of patterned burst and interburst interval on the excitation‐coupling mechanism in the isolated rat neural lobe. , 1985, The Journal of physiology.

[28]  T. Higuchi,et al.  Release of oxytocin during suckling and parturition in the rat. , 1985, The Journal of endocrinology.

[29]  J. Yamada,et al.  Transgenic expression of enhanced green fluorescent protein enables direct visualization for physiological studies of vasopressin neurons and isolated nerve terminals of the rat. , 2005, Endocrinology.

[30]  K. Yagi,et al.  Differential effects of naloxone on neuroendocrine responses to fear-related emotional stress , 2004, Experimental Brain Research.

[31]  Andras Nagy,et al.  The color of mice: in the light of GFP-variant reporters , 2001, Histochemistry and Cell Biology.

[32]  G. Dayanithi,et al.  Relaxin affects the release of oxytocin and vasopressin from the neurohypophysis , 1987, Nature.