| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Animal Model |
From the Renal Division and Department of Medicine,*
St.
Michael’s Hospital and University of Toronto, Toronto, Ontario,
Canada; the Department of Pathology,
Hospital
for Sick Children, Toronto, Ontario, Canada; and the Institute of
Anatomy,
University of Hamburg,
Hamburg, Germany
Neuronal nitric oxide synthase (nNOS) plays a modulatory role in the biology of a variety of neuroendocrine tissues and is especially relevant to gonadal function. We have previously reported the cloning and characterization of a variant of the nNOS protein, termed testis nNOS (TnNOS), the mRNA for which was restricted in expression to male gonadal tissues. To examine the cell-specificity of the testis-specific NOS regulatory regions we defined patterns of ß-galactosidase expression of an insertional transgene in which the reporter gene lacZ was under the transcriptional control of the human TnNOS promoter. ß-galactosidase activity was detected exclusively in the interstitial cells of the testis in transgenic mice. These cells also evidenced positive staining for nNOS protein and were identified as androgen-producing Leydig cells by staining with the Leydig cell marker, P450scc. Expression of the promoter was absent in cells of the seminiferous tubules, specifically germline cells of different stages and Sertoli cells. In contrast to the male gonad, ß-galactosidase activity was not detected in ovaries of adult female mice. Activity was also not evident in organs known to express full-length nNOS, such as skeletal muscle, kidney, or cerebellum. The same pattern of ß-galactosidase staining was observed in independent transgenic founders and was distinct from that observed for an endothelial NOS promoter/reporter transgene. In the testis of male adult eNOS promoter-reporter transgenic mice, ß-galactosidase activity was expressed only in endothelial cells of large- and medium-sized arterial blood vessels. Transcriptional activity of the human TnNOS promoter could not be detected in a variety of cell types, including Leydig cells, using episomal promoter-reporter constructs suggesting that a nuclear environment and higher order genomic complexity are required for appropriate promoter function. The restricted expression pattern of an nNOS variant in Leydig cells of the male gonad suggests an important role in the regulation of testosterone release and represents an intriguing model with which to dissect the molecular basis of Leydig cell-specific gene expression.
This article has been cited by other articles:
 |
|
 |
|
  S. Weber, D. Eckert, D. Nettersheim, A. J.M. Gillis, S. Schafer, P. Kuckenberg, J. Ehlermann, U. Werling, K. Biermann, L. H.J. Looijenga, et al. Critical Function of AP-2gamma/TCFAP2C in Mouse Embryonic Germ Cell Maintenance Biol Reprod, January 1, 2010; 82(1): 214 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Nagl, K. Schonhofer, B. Seidler, J. Mages, H.-D. Allescher, R. M. Schmid, G. Schneider, and D. Saur Retinoic acid-induced nNOS expression depends on a novel PI3K/Akt/DAX1 pathway in human TGW-nu-I neuroblastoma cells Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1146 - C1156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mondillo, R. M. Pagotto, B. Piotrkowski, C. G. Reche, Z. J. Patrignani, C. B. Cymeryng, and O. P. Pignataro Involvement of Nitric Oxide Synthase in the Mechanism of Histamine-Induced Inhibition of Leydig Cell Steroidogenesis via Histamine Receptor Subtypes in Sprague-Dawley Rats Biol Reprod, January 1, 2009; 80(1): 144 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kondo, T. Ishikawa, K. Yamaguchi, T. Yada, and M. Fujisawa Oral Administration of Tetrahydrobiopterin Attenuates Testicular Damage by Reducing Nitric Oxide Synthase Activity in a Cryptorchid Mouse Model J Androl, March 1, 2008; 29(2): 153 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. X. L. Zhang, T. R. Searcy, Y. Wu, D. Gozal, and Y. Wang Alternative promoter usage and alternative splicing contribute to mRNA heterogeneity of mouse monocarboxylate transporter 2 Physiol Genomics, December 19, 2007; 32(1): 95 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tokuda, Y. Kadokawa, H. Kurahashi, and T. Marunouchi CDH1 Is a Specific Marker for Undifferentiated Spermatogonia in Mouse Testes Biol Reprod, January 1, 2007; 76(1): 130 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Herman and C. Rivier Activation of a Neural Brain-Testicular Pathway Rapidly Lowers Leydig Cell Levels of the Steroidogenic Acute Regulatory Protein and the Peripheral-Type Benzodiazepine Receptor while Increasing Levels of Neuronal Nitric Oxide Synthase Endocrinology, January 1, 2006; 147(1): 624 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ishikawa, Y. Kondo, K. Goda, and M. Fujisawa Overexpression of Endothelial Nitric Oxide Synthase in Transgenic Mice Accelerates Testicular Germ Cell Apoptosis Induced by Experimental Cryptorchidism J Androl, March 1, 2005; 26(2): 281 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. P.Y. Lee and C. Y. Cheng Nitric Oxide/Nitric Oxide Synthase, Spermatogenesis, and Tight Junction Dynamics Biol Reprod, February 1, 2004; 70(2): 267 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. K. Bachir, G. Garrel, A. Lozach, J.-N. Laverriere, and R. Counis The Rat Pituitary Promoter of the Neuronal Nitric Oxide Synthase Gene Contains an Sp1-, LIM Homeodomain-Dependent Enhancer and a Distinct Bipartite Gonadotropin-Releasing Hormone-Responsive Region Endocrinology, September 1, 2003; 144(9): 3995 - 4007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Newton, S. C. Bevan, S. Choi, G. B. Robb, A. Millar, Y. Wang, and P. A. Marsden Translational Regulation of Human Neuronal Nitric-oxide Synthase by an Alternatively Spliced 5'-Untranslated Region Leader Exon J. Biol. Chem., January 3, 2003; 278(1): 636 - 644. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
