Skip to main content
SpringerLink
Log in

Transgenic and Transcriptional Studies on Neurosecretory Cell Gene Expression

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

1. Studies of the regulation of neurosecretory cell gene expression suffer from the lack of suitable cell lines. Two approaches have been used to overcome this deficit: transfection of neuropeptide genes into heterologous cell lines and generation of transgenic animals.

2. Studies with heterologous cell lines have revealed the potential involvement of nuclear hormone receptors, POU proteins, and fos/jun/ATF family members in the regulation of the vasopressin and oxytocin genes. Although limited in their scope, these studies have contributed greatly to the dissection of basic properties of elements in the vasopressin and oxytocin gene promoters.

3. Transgenic mice, and more recently rats, have been used to elucidate genomic regions governing cell specificity and physiological regulation of neurosecretory gene expression. The genes encoding the neuropeptides vasopressin and oxytocin have been used in many transgenic studies, due to the well-defined expression patterns and physiology of the endogenous neuropeptides. Cell-specific and physiologically regulated expression of these transgenes has been achieved, demonstrating the action of putative represser elements and regulation of the expression of one gene by sequences present in the other gene.

4. Appropriate expression and translation of transgenes have resulted in the production of several useful systems. Expression of oncogene sequences in gonadotropin-releasing hormone neurons has allowed the development of cell lines from the resulting tumors, overproduction of corticotropin-releasing factor has produced animal models of anxiety and obesity, and directed ectopic expression of growth hormone has generated a potentially useful rat model of dwarfism. These and other animal models of human disease will provide important avenues for the development of therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Adan, R. A. H., and Burbach, J. P. H. (1992). Regulation of vasopressin and oxytocin gene expression by estrogen and thyroid hormones. Prog. Brain Res. 92:127–136.

    Google Scholar 

  • Adan, R. A. H., Walther, N., Cox, J. J., Ivell, R., and Burbach, J. P. H. (1991). Comparison of the estrogen responsiveness of the rat and bovine oxytocin promoters. Biochem. Biophys. Res. Commun. 175:117–122.

    Google Scholar 

  • Adan, R. A. H., Cox, J. J., Kats, J. P., and Burbach, J. P. H. (1992). Thyroid hormone regulates the oxytocin gene. J. Biol. Chem. 267:3771–3777.

    Google Scholar 

  • Adan, R. A. H., Cox, J. J., Beischlag, T. V., and Burbach, J. P. H. (1993). A composite hormone response element mediates the transaction of the rat oxytocin gene by different classes of nuclear hormone receptors. Mol. Endocrinol. 7:47–57.

    Google Scholar 

  • Ang, H.-L., Carter, D. A., and Murphy, D. (1993). Neuron-specific expression and physiological regulation of bovine vasopressin transgenes in mice. EMBO J. 12:2397–2409.

    Google Scholar 

  • Axelrod, J., and Reisine, T. D. (1984). Stress hormones: Their interaction and regulation. Science 224:452–459.

    Google Scholar 

  • Axelson, J. F., and Van Leeuwen, F. W. (1990). Differential localization of estrogen receptors in various vasopressin synthesizing nuclei of rat brain. J. Neuroendocrinol. 2:209–216.

    Google Scholar 

  • Banerjee, S. A., Roffler-Tarlov, S., Szabo, M., Frohman, L., and Chikaraishi, D. M. (1994). DNA regulatory sequences of the rat tyrosine hydroxylase gene direct correct catecholaminergic cell-type specificity of a human growth hormone reporter in the CNS of transgenic mice causing a dwarf phenotype. Mol. Brain Res. 24:89–106.

    Google Scholar 

  • Beato, M. (1989). Gene regulation by steroid hormones. Cell 56:335–344.

    Google Scholar 

  • Behringer, R. R., Matthews, L. S., Palmiter, R. D., and Brinster, R. L. (1988). Dwarf mice produced by genetic ablation of growth hormone-expressing cells. Genes Dev. 2:453–461.

    Google Scholar 

  • Belenky, M., Castel, M., Young, W. S., III, Gainer, H., and Cohen, S. (1992). Ultrastructural immunolocalisation of rat oxytocin-neurophysin in transgenic mice expressing the rat oxytocin gene. Brain Res. 583:279–286.

    Google Scholar 

  • Bradley, D. J., Young, W., III, and Weinberger, C. (1989). Differential expression of and thyroid hormone receptor genes in rat brain and pituitary. Proc. Natl. Acad. Sci. USA 86:7250–7254.

    Google Scholar 

  • Burbach, J. P. H., and Adan, R. A. H. (1993). The rat oxytocin gene. Physiological changes in expression in the hypothalamo-neurohypophysial system and responsiveness of promoter activity. Ann. N.Y. Acad. Sci. 689:34–49.

    Google Scholar 

  • Burbach, J. P. H., De Hoop, M. J., Schmale, H., Richter, D., De Kloet, E. R., Ten Haaf, J. A., and De Wied, D. (1984). Differential responses to osmotic stress of vasopressin-neurophysin mRNA in hypothalamic nuclei. Neuroendocrinology 39:582–584.

    Google Scholar 

  • Burbach, J. P. H., Adan, R. A. H., Van Tol, H. H. M., Verbeeck, M. A. E., Axelson, J. F., Van Leeuwen, F. W., Beekman, J. M., and Ab, G. (1990). Regulation of the rat oxytocin gene by estradiol. J. Neuroendocrinol. 2:633–639.

    Google Scholar 

  • Burbach, J. P. H., Lopes, Da Silva, S., Cox, J. J., Adan, R. A. H., Cooney, A. J., Tsai, M.-J., and Tsai, S. Y. (1994). Repression of estrogen-dependent stimulation of the oxytocin gene by COUP transcription factor I. J. Biol. Chem. 269:15046–15053.

    Google Scholar 

  • Carey, R. M., Varma, S. K., Drake, C. R., Thorner, M. O., Lovacs, K., Rivier, J., and Vale, W. (1984). Ectopic secretion of corticotrophin-releasing factor as a cause of Cushing's syndrome. N. Engl. J. Med. 311:13–20.

    Google Scholar 

  • Chambers, T. J., Owens, J. M., Hattersley, G., Jat, P. S., and Noble, M. D. (1993). Generation of osteoclast-inductive and osteoclastogenic cell lines from the H-2KbA58 transgenic mouse. Proc. Natl. Acad. Sci. USA 90:5578–5582.

    Google Scholar 

  • Chang, C., Lopes Da Silva, S., Ideta, R., Lee, Y., Yeh, S., and Burbach, J. P. H. (1994). Human and rat TR4 orphan receptors specify a subclass of the steroid receptor superfamily. Proc. Natl. Acad. Sci. USA 91:6040–6044.

    Google Scholar 

  • Charlton, H. M., Clark, R. G., Robinson, I. C. A. F., Goff, A. E., Cox, B. S., Bugnon, C., and Bloch, B. A. (1988). Growth hormone-deficient dwarfism in the rat: A new mutation. J. Endocrinol. 119:51–58.

    Google Scholar 

  • Clark, R. G., Chambers, G., Lewin, J., and Robinson, I. C. A. F. (1986). Automated repetitive microsampling of blood: Growth hormone profiles in conscious male rats. J. Endocrinol. 111:27–35.

    Google Scholar 

  • Dale, H. H. (1906). On some physiological actions of ergot. J. Physiol. 34:165–206.

    Google Scholar 

  • Earnest, D. J., and Sladek, C. D. (1986). Circadian rhythms of vasopressins release from individual rat suprachiasmatic explants in vitro. Brain Res. 382:129–133.

    Google Scholar 

  • Eicher, E. M., and Beamer, W. G. (1976). Inherited ateliotic dwarfism in mice. Characteristics of the mutation, little, in chromosome 6. J. Hered. 67:87–91.

    Google Scholar 

  • Faus, I., Hsu, H. J., and Fuchs, E. (1994). Oct-6: A regulator of keratinocyte gene expression in stratified squamous epithelia. Mol. Cell. Biol. 14:3263–3275.

    Google Scholar 

  • Fitzsimmons, M. D., Roberts, M. M., Sherman, T. G., and Robinson, A. G. (1992). Models of neurohypophyseal homeostasis. Am. J. Physiol. 262:R1121–R1130.

    Google Scholar 

  • Fitzsimmons, M. D., Roberts, M. M., and Robinson, A. G. (1994). Control of posterior pituitary vasopressin content: Implications for the regulation of the vasopressin gene. Endocrinology 134:1874–1878.

    Google Scholar 

  • Flavell, D. M., Wells, T., Wells, S. E., Carmignac, D. F., Thomas, G. B., and Robinson, I. C. A. F. (1995). A new dwarf rat I: Dominant negative phenotype in GRF-GH transgenic growth retarded (Tgr) rats. 77th Annual Meeting, U.S. Endocrine Society, Washington, DC, P2–239.

  • Flavell, D. M., Wells, T., Wells, S. E., Carmignac, D. F., Thomas, G. B., and Robinson, I. C. A. F. (1996). Dominant dwarfism in transgenic rats by targeting human growth hormone (GH) expression to hypothalamic GH-releasing factor neurons. EMBO J. 15:3871–3879.

    Google Scholar 

  • Fletcher, J. M. (1986). Effects of adrenalectomy before weaning in the genetically obese Zucker rat (fa/fa). Br. J. Nutr. 56:141–151.

    Google Scholar 

  • Friemann, A. S., Fay, M. J., and North, W. G. (1995). Factors regulating the production of human vasopressin-associated neurophysin by small-cell carcinoma of the lung: Evaluation by computer-enhanced quantitative immunocytochemistry. Neuropeptides 28:183–189.

    Google Scholar 

  • Gainer, H. (1995). Strategies for cell biological studies in oxytocinergic neurons. In Ivell, R. (ed.), Oxytocin: Cellular and Molecular Approaches in Medicine and Research, Plenum Press.

  • Gainer, H., and Wray, S. (1994). Cellular and molecular biology of oxytocin and vasopressin. In Knobil, E., and Neill, J. D. (eds.), The Physiology of Reproduction, 2nd ed., Raven Press, New York, pp. 1099–1129.

    Google Scholar 

  • Gold, P. W., Goodwin, F. K., and Chrousos, G. P. (1988). Clinical and biochemical manifestations of depression. N. Engl. J. Med. 319:413–420.

    Google Scholar 

  • Grant, F. D., Reventos, J., Gordon, J. W., Kawabata, S., Miller, M., and Majzoub, J. A. (1993). Expression of the rat arginine vasopressin gene in transgenic mice. Mol. Endocrinol. 7:659–667.

    Google Scholar 

  • Groves, A. K., Entwistle, A., Jat, P. S., and Noble, M. (1993). The characterisation of astrocyte cell lines that display properties of glial scar tissue. Dev. Biol. 159:87–104.

    Google Scholar 

  • Gura, T. (1995). Antisense has growing pains. Science 270:575–577.

    Google Scholar 

  • Hammer, G. D., Fairchild-Huntress, V., and Low, M. J. (1990). Pituitary-specific and hormonally regulated gene expression directed by the rat proopiomelanocortin promoter in transgenic mice. Mol. Endocrinol. 4:1689–1697.

    Google Scholar 

  • Hara, Y., Battey, J., and Gainer, H. (1990). Structure of mouse vasopressin and oxytocin genes. Mol. Brain Res. 8:319–324.

    Google Scholar 

  • He, X., Treacy, M. N., Simmons, D. M., Ingraham, H. A., Swanson, L. W., and Rosenfeld, M. G. (1989). Expression of a large family of POU-domain regulatory genes in mammalian brain development. Nature 340:35–42.

    Google Scholar 

  • He, X., Gerrero, R., Simmons, D. M., Park, R. E., Lin, C. R., Swanson, L. W., and Rosenfeld, M. G. (1991). Tst-1, a member of the POU domain gene family, binds the promoter of the gene encoding the cell surface adhesion molecule Po. Mol. Cell Biol. 11:1739–1733.

    Google Scholar 

  • Ho, M.-Y., Carter, D. A., Ang, H.-L., and Murphy, D. (1995). Bovine oxytocin transgenes in mice. Hypothalamic expression, physiological regulation, and interactions with the vasopressin gene. J. Biol. Chem. 270:27199–27205.

    Google Scholar 

  • Hollingshead, P. G., Martin, L., Pitts, S. L., and Stewart, T. A. (1989). A dominant phenocopy of hypopituitarism in transgenic mice resulting from central nervous system synthesis of human growth hormone. Endocrinology 125:1556–1564.

    Google Scholar 

  • Ivell, R., and Richter, D. (1984). Structure and comparison of the oxytocin and vasopressin genes from rat. Proc. Natl. Acad. Sci. USA 81:2006–2010.

    Google Scholar 

  • Jat, P. S., Noble, M. D., Ataliotis, P., Tanaka, Y., Yannoutsos, N., Larssen, L., and Kioussis, D. (1991). Direct derivation of conditionally immortal cell lines from an H-2Kb-tsA58 transgenic mouse. Proc. Natl. Acad. Sci. USA 88:5096–5100.

    Google Scholar 

  • Kendall, S. K., Saunders, T. L., Jin, L., Lloyd, R. V., Glode, L. M., Nett, T. M., Keri, R. A., Nilson, J. H., and Camper, S. A. (1991). Targeted ablation of pituitary gonadotropes in transgenic mice. Mol. Endocrinol. 5:2025–2036.

    Google Scholar 

  • Kraner, S. D., Chong, J. A., Tsay, H.-J., and Mandel, G. (1992). Silencing the type II sodium channel gene: A model for neural-specific gene regulation. Neuron 9:37–44.

    Google Scholar 

  • Lefebvre, D. L., Giaid, A., Bennett, H., Larivière, R., and Zingg, H. (1992). Oxytocin gene expression in rat uterus. Science 256:1553–1555.

    Google Scholar 

  • Le Moine, C., and Young, W. S. (1992). RHS2, a POU domain-containing gene, and its expression in developing and adult rat. Proc. Natl. Acad. Sci. USA 89:3285–3289.

    Google Scholar 

  • Li, L., Suzuki, T., Mori, N., and Greengard, P. (1993). Identification of a functional silencer element involved in neuron-specific expression of the synapsin I gene. Proc. Natl. Acad. Sci. USA 90:1460–1464.

    Google Scholar 

  • Li, P., He, X., Gerrero, M. R., Mok, M., Aggarwal, A., and Rosenfeld, M. G. (1993). Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors. Genes Dev. 7:2483–2496.

    Google Scholar 

  • Li, S., Crenshaw, E. B., Rawson, E. J., Simmons, D. M., Swanson, L. W., and Rosenfeld, M. G. (1990). Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature 347:528–533.

    Google Scholar 

  • Liebhaber, S. A., Russell, J. E., Cash, F. E., and Eshleman, S. S. (1992). Inhibition of messenger RNA translation by antisense sequences. Gene Regul. 1:163–174.

    Google Scholar 

  • Lipkin, S. M., Nelson, C. A., Glass, C. K., and Rosenfeld, M. G. (1992). A negative retinoic acid response element in the rat oxytocin promoter restricts transcriptional stimulation by heterologous transactivation domains. Proc. Natl. Acad. Sci. USA 89:1209–1213.

    Google Scholar 

  • Lopes da Silva, S., and Burbach, J. P. H. (1995). The nuclear hormone receptor family in the brain: Classics and orphans. Trends Neurosci. 18:542–548.

    Google Scholar 

  • Lopes da Silva, S., Van Horssen, A. M., Chang, C., and Burbach, J. P. H. (1995). Expression of nuclear hormone receptors in the rat supraoptic nucleus. Endocrinology 136:2276–2283.

    Google Scholar 

  • Martinou, J.-C., Dubois-Dauphin, M., Staple, J. K., Rodriguez, I., Frankowski, H., Missotten, M., Albertini, P., Talabot, D., Catsicas, S., Pietra, C., and Huarte, J. (1994). Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13:1017–1030.

    Google Scholar 

  • Mathis, J. M., Simmons, D. M., He, X., Swanson, L. W., and Rosenfeld, M. G. (1992). Brain 4: A novel mammalian POU transcription factor exhibiting restricted brain-specific expression. EMBO J. 11:2551–2561.

    Google Scholar 

  • Mellon, P. L., Windle, J. J., Goldsmith, P. C., Padula, C. A., Roberts, J. L., and Weiner, R. I. (1990). Immortalisation of hypothalamic GnRH neurons by genetically targeted tumourigenesis. Neuron 5:1–10.

    Google Scholar 

  • Mohr, E., and Schmitz, E. (1991). Functional characterisation of estrogen and glucocorticoid responsive elements in the rat oxytocin gene. Mol. Brain Res. 9:293–298.

    Google Scholar 

  • Mohr, E., Bahnsen, U., Kiessling, C., and Richter, D. (1988a). Expression of the vasopressin and oxytocin genes occurs in mutually exclusive sets of hypothalamic neurons. FEBS Lett. 242:144–148.

    Google Scholar 

  • Mohr, E., Schmitz, E., and Richter, D. (1988b). A single rat genomic DNA fragment encodes both the oxytocin and vasopressin genes separated by 11 kilobases and oriented in opposite transcriptional directions. Biochimie 70:70–74.

    Google Scholar 

  • Monuki, E. S., Kuhn, R., Weinmaster, B. D. T., and Lemke, G. (1990). Expression and activity of the POU transcription factor SCIP. Science 249:1300–1303.

    Google Scholar 

  • Morgan, J. E., Beauchamp, J. R., Peckham, M., Ataliotis, P., Nat, P., Noble, M., Farmer, K., and Partridge, T. (1994). Myogenic cells derived from H-2KbtsA58 transgenic mice are conditionally immortal in vitro but differentiate normally in vivo. Dev. Biol. 162:486–498.

    Google Scholar 

  • Mori, N., Stein, R., Sugmund, O., and Anderson, D. A. (1990). A cell type-preferred silencer element that controls the neural-specific expression of the SCG10 gene. Neuron 4:583–594.

    Google Scholar 

  • Mori, N., Schoenherr, C., Vandenbergh, D. J., and Anderson, D. J. (1992). A common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells. Neuron 9:45–54.

    Google Scholar 

  • Muglia, L., Jacobson, L., Dikkes, P., and Majzoub, J. A. (1995). Corticotropin-releasing hormone deficiency reveals a major fetal but not adult glucocorticoid need. Nature 373:427–432.

    Google Scholar 

  • Nakai, S., Kawano, H., Yudate, T., Nishi, M., Kuno, J., Nagata, A., Jishage, K., Hamada, H., Fujii, H., Kawamura, K., Shiba, K., and Noda, T. (1995). The POU domain transcription factor Brn-2 is required for the determination of specific neuronal lineages in the hypothalamus of the mouse. Genes Dev. 9:3109–3121.

    Google Scholar 

  • Noble, M., Groves, A. K., Ataliotis, P., Ikram, Z., and Jat, P. S. (1995). The H-2KbtsA58 transgenic mouse: A new tool for the rapid generation of novel cell lines. Transgen. Res. 4:215–225.

    Google Scholar 

  • Ornitz, D. M., Hammer, R. E., Messing, A., Palmiter, R. D., and Brinster, R. L. (1987). Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science 238:188–193.

    Google Scholar 

  • Ott, I., and Scott, J. C. (1911). The action of infundibulin upon mammary secretion. Proc. Soc. Exp. Biol. Med. 8:48–49.

    Google Scholar 

  • Pardy, K., Adan, R. A. H., Carter, D., Seah, V., Burbach, J. P. H., and Murphy, D. (1992). The identification of a cis-acting element involved in cyclic 3′,5′-adenosine monophosphate regulation of bovine vasopressin gene expression. J. Biol. Chem. 267:21746–21752.

    Google Scholar 

  • Parker, M. G. (1993). Steroid and related receptors. Curr. Opin. Cell Biol. 5:499–504.

    Google Scholar 

  • Pepin, M.-C., Pothier, F., and Barden, N. (1992a). Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression. Mol. Pharmacol. 42:991–995.

    Google Scholar 

  • Pepin, M.-C., Pothier, F., and Barden, N. (1992b). Impaired type II glucocorticoid-receptor function in mice bearing antisense RNA transgene. Nature 355:725–728.

    Google Scholar 

  • Radovick, S., Wray, S., Lee, E., Nicols, D. K., Nakayama, Y., Weintraub, B. D., Westphal, B. D., Cutler, G. B., Jr., and Wondisford, F. E. (1991). Migratory arrest of gonadotropin-releasing hormone neurons in transgenic mice. Proc. Natl. Acad. Sci. USA 88:3402–3406.

    Google Scholar 

  • Renaud, L. P., and Bourque, C. W. (1991). Neurophysiology and neuropharmacology of hypothalamic magnocellular neurons secreting vasopressin. Prog. Neurobiol. 36:131–169.

    Google Scholar 

  • Richard, S., and Zingg, H. H. (1990). The human oxytocin gene promoter is regulated by estrogen. J. Biol. Chem. 265:6098–6103.

    Google Scholar 

  • Richard, S., and Zingg, H. H. (1991). Identification of a retinoic acid response element in the human oxytocin promoter. J. Biol. Chem. 266:21428–21433.

    Google Scholar 

  • Rivier, C., and Vale, W. (1983). Modulation of stress-induced ACTH release by corticotrophin-releasing factor, catecholamines and vasopressin. Nature 305:325–327.

    Google Scholar 

  • Robinson, A. G. (1974). Elevation of plasma neurophysin in women on oral contraceptives. J. Clin. Invest. 54:209–212.

    Google Scholar 

  • Robinson, A. G., Haluszczak, C., Wilkins, J. A., Huellmantel, A. B., and Watson, C. G. (1977). Physiological control of two neurophysins in humans. J. Clin. Endocrinol. Metab. 44:330–339.

    Google Scholar 

  • Rubinstein, M., Mortrud, M., Liu, B., and Low, M. J. (1993). Rat and mouse proopiomelanocortin gene sequences target tissue-specific expression to the pituitary gland but not to the hypothalamus of transgenic mice. Neuroendocrinology 58:373–380.

    Google Scholar 

  • Ruppert, S. D., Scherer, G., and Schutz, G. (1984). Recent gene conversion involving bovine vasopressin and oxytocin precursor genes suggested by nucleotide sequence. Nature 308:554–557.

    Google Scholar 

  • Sausville, E., Carney, D., and Battey, J. (1985). The human vasopressin gene is linked to the oxytocin gene and is selectively expressed in a cultured lung cancer cell line. J. Biol. Chem. 260:10236–10241.

    Google Scholar 

  • Schedl, A., Larin, Z., Montoliu, L., Thies, E., Kelsey, G., Lehrach, H., and Schultz, G. (1993a). A method for the generation of YAC transgenic mice by pronuclear microinjection. Nucleic Acids Res. 21:4783–4787.

    Google Scholar 

  • Schedl, A., Montoliu, L., Kelsey, G., and Schutz, G. (1993b). A yeast artificial chromosome covering the tyrosinase gene confers copy number-dependent expression in transgenic mice. Nature 362:258–261.

    Google Scholar 

  • Schoenherr, C. J., and Anderson, D. J. (1995). The neuron-restrictive silencer factor (NSRF): A coordinate repressor of multiple neuron-specific genes. Science 267:1360–1363.

    Google Scholar 

  • Schonemann, M. D., Ryan, A., McEvilly, R. J., O'Connell, S. M., Arias, C. A., Kalla, K. A., Li, P., Sawchenko, P. E., and Rosenfeld, M. G. (1995). Development and survival of the endocrine hypothalamus and posterior pituitary gland requires the neuronal POU domain factor Brn-2. Genes Dev. 9:3122–3135.

    Google Scholar 

  • Sherman, T. G. (1996). Transcriptional regulation of the vasopressin gene. Curr. Opin. Endocrinol. Diabetes 3:178–183.

    Google Scholar 

  • Stenzel-Poore, M. P., Cameron, V. A., Vaughan, J., Sawchenko, P. E., and Vale, W. (1992). Development of Cushing's syndrome in corticotrophin-releasing factor transgenic mice. Endocrinology 130:3378–3386.

    Google Scholar 

  • Stenzel-Poore, M. P., Heinrichs, S. C., Rivest, S., Koob, G. F., and Vale, W. W. (1994). Overproduction of corticotrophin releasing factor in transgenic mice: A genetic model of anxiolytic behaviour. J. Neurosci. 14:2579–2584.

    Google Scholar 

  • Suri, C., Fung, B. P., Tischler, A. S., and Chikaraishi, D. M. (1993). Catecholaminergic cell lines from the brain and adrenal glands of tyrosine-hydroxylase-SV40 T antigen transgenic mice. J. Neurosci. 13:1280–1291.

    Google Scholar 

  • Suzuki, N., Rohdewohld, T. N., Gruss, P., and Schöler, H. R. (1990). Oct-6: A POU transcription factor expressed in embryonal stem cells and in the developing brain. EMBO J. 9:3723–3732.

    Google Scholar 

  • Swanson, L. W. (1992). Spatiotemporal patterns of transcription factor gene expression accompanying the development and plasticity of cell phenotypes in the neuroendocrine system. Prog. Brain Res. 92:97–113.

    Google Scholar 

  • Takeuchi, T., Suzuki, H., Sakurai, S., Nogami, H., Okuma, S., and Ishikawa, H. (1990). Molecular mechanism of growth hormone (GH) deficiency in the spontaneous dwarf rat: Detection of abnormal splicing of GH messenger ribonucleic acid by the polymerase chain reaction. Endocrinology 126:31–38.

    Google Scholar 

  • Uhl, G. R., and Reppert, S. M. (1986). Suprachiasmatic nucleus vasopressin messenger RNA: Circadian variation in normal and Brattleboro rats. Science 232:390–393.

    Google Scholar 

  • Umesono, K., Murakami, K. K., Thompson, C. C., and Evans, R. M. (1991). Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell 65:1255–1266.

    Google Scholar 

  • van Tol, H. H. M., Bolwerk, E. L. M., Liu, B., and Burbach, J. P. H. (1988). Oxytocin and vasopressin gene expression in the hypothalamo-neurohypophyseal system of the rat during the estrous cycle, pregnancy and lactation. Endocrinology 122:945–951.

    Google Scholar 

  • Verbeeck, M. A. E., Sutanto, W., and Burbach, J. P. H. (1991). Regulation of vasopressin messenger RNA levels in the small cell lung carcinoma cell line GLC-8: Interactions between glucocorticoids and second messengers. Mol. Endocrinol. 5:796–801.

    Google Scholar 

  • Verbeeck, M. A. E., Mummery, C. L., Feijen, A., and Burbach, J. P. H. (1992a). Survey of neuropeptide gene expression in tumor cell lines. Pathobiology 60:127–135.

    Google Scholar 

  • Verbeeck, M. A. E., Burbach, J. P. H., Elands, J. P. M., De Leij, L. F. M. H., Buys, C. H. C. M., Carney, D. N., Bepler, G., Roebroek, A. J. M., and Van de Ven, W. J. M. (1992b). Expression of the vasopressin and gastrin-releasing peptide genes in small cell lung carcinoma cell lines. Pathobiology 60:136–142.

    Google Scholar 

  • Wagner, R. W. (1994). Gene inhibition using antisense oligodeoxynucleotides. Nature 372:333–335.

    Google Scholar 

  • Waller, S. J., and Murphy, D. (1995). Expression of rat vasopressin transgenes in rats. In Saito, T., Kurokawa, K., and Yoshida, S. (eds.), Neurohypophysis: Recent Progress of Vasopressin and Oxytocin Research, Excerpta Medica Congress Series 1098, Elsevier, Amsterdam, pp. 89–98.

    Google Scholar 

  • Waller, S. J., Ho, M.-Y., and Murphy, D. (1995). Production of transgenic rodents by microinjection of cloned DNA into fertilised one-cell eggs. In Glover, D. M., and Hames, B. D. (eds.), DNA Cloning 4: Mammalian Systems, Oxford University Press, Oxford, pp. 185–229.

    Google Scholar 

  • Waller, S. J., Fairhall, K. M., Xu, J., Robinson, I. C. A. F., and Murphy, D. (1996). Neurohypophyseal and fluid homeostasis in transgenic rats expressing a tagged rat vasopressin prepropeptide in vasopressinergic magnocellular neurons. 137:5068–5077.

    Google Scholar 

  • Walther, N., Wehrenberg, U., Brackmann, B., and Ivell, R. (1991). Mapping of the bovine oxytocin gene control region: Identification of binding sites for luteal nuclear proteins in the 5 non-coding region of the gene. J. Neuroendocrinol. 3:539–549.

    Google Scholar 

  • Wegner, M., Drolet, D. W., and Rosenfeld, M. G. (1993). Regulation of JC virus by the poudomain transcription factor Tst-1: Implications for progressive multifocal leukoencephalopathy. Proc. Natl. Acad. Sci. USA 90:4743–4747.

    Google Scholar 

  • Wehrenberg, U., Ivell, R., and Walther, N. (1992). The COUP transcription factor (COUP-TF) is directly involved in the regulation of oxytocin gene expression in luteinizing bovine granulosa cells. Biochem. Biophys. Res. Commun. 189:496–503.

    Google Scholar 

  • Wehrenberg, U., Ivell, R., Jansen, M., VonGoedecke, S., and Walther, N. (1994a). Two orphan receptors binding to a common site are involved in the regulation of the oxytocin gene in the bovine ovary. Proc. Natl. Acad. Sci. USA 91:1440–1444.

    Google Scholar 

  • Wehrenberg, U., VonGoedecke, S., Ivell, R., and Walther, N. (1994b). The orphan receptor SF-1 binds to the COUP-like element in the promoter of the actively transcribed oxytocin gene. J. Neuroendocrinol. 6:1–4.

    Google Scholar 

  • Wells, T., Flavell, D. M., Wells, S. E., Carmignac, D. F., and Robinson, I. C. A. F. (1995). A new dwarf rat II: GH secretion, responses to GRF and somatostatin, and growth stimulation by GRF in the GRF-GH transgenic (Tgr) rat. 77th Annual Meeting, U.S. Endocrine Society, Washington, DC, P2–240.

  • Wetsel, W. C., Eraly, S. A., Whyte, D. B., and Mellon, P. L. (1993). Regulation of gonadotropin-releasing hormone by protein kinase-A and-C in immortalised hypothalamic neurons. Endocrinology 132:2360–2370.

    Google Scholar 

  • Whyte, D. B., Lawson, M. A., Belsham, D. D., Eraly, S. A., Bond, C. T., Adelman, J. P., and Mellon, P. L. (1995). A neuron-specific enhancer targets expression of the gonadotropin-releasing hormone gene to hypothalamic neurosecretory neurons. Mol. Endocrinol. 9:467–477.

    Google Scholar 

  • Wierman, M. E., Bruder, J. M., and Kepa, J. K. (1995). Regulation of gonadotropin-releasing hormone gene expression in hypothalamic neuronal cells. Cell. Mol. Neurobiol. 15:79–88.

    Google Scholar 

  • Windle, J. J., Weiner, R. I., and Mellon, P. L. (1990). Cell lines of the pituitary gonadotrope lineage derived by targeted oncogenesis in transgenic mice. Mol. Endocrinol. 4:597–603.

    Google Scholar 

  • Wray, S., Kusano, K., and Gainer, H. (1991). Maintenance of LHRH and oxytocin neurons in slice explants cultured in serum-free media: effects of tetrodotoxin on gene expression. Neuroendocrinology 54:327–339.

    Google Scholar 

  • Young, W. S., Reynolds, K., Shepard, E. A., Gainer, H., and Castel, M. (1990). Cell specific expression of the rat oxytocin gene in transgenic mice. Neuroendocrinology 2:917–925.

    Google Scholar 

  • Zeng, Q., Carter, D. A., and Murphy, D. (1994a). Cell specific expression of a vasopressin transgene in rats. J. Neuroendocrinol. 6:469–477.

    Google Scholar 

  • Zeng, Q., Foo, N.-C., Funkhouser, J. M., Carter, D. A., and Murphy, D. (1994b). Expression of a rat vasopressin transgene in rat testis. J. Reprod. Fert. 102.

  • Zingg, H. H., Lefebrve, D. L., and Almazan, G. (1986). Regulation of vasopressin gene expression in hypothalamic neurons. J. Biol. Chem. 261:12956–12959.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuropeptide Laboratory, Institute of Molecular and Cell Biology, 10 Kent Ridge Crescent, Singapore, 119260, Republic of Singapore

    Anil Ratty & David Murphy

  2. Rudolf Magnus Institute, Department of Medical Pharmacology, Utrecht University, P.O. Box 80040, 3508 TA, Utrecht, The Netherlands

    J. Peter H. Burbach

  3. Department of Medicine, Bristol Royal Infirmary, Bristol University, Bristol, BS2 8HW, UK

    David Murphy

Authors
  1. Sarah Jane Waller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anil Ratty
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Peter H. Burbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Waller, S.J., Ratty, A., Burbach, J.P.H. et al. Transgenic and Transcriptional Studies on Neurosecretory Cell Gene Expression. Cell Mol Neurobiol 18, 149–171 (1998). https://doi.org/10.1023/A:1022512819023

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022512819023

Search

Navigation