| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Testis |
Departments of Molecular Genetics and Microbiology,3
Pharmacological Sciences,4
Obstetrics and Gynecology,5 State University of New York at Stony Brook, Stony Brook, New York 11794
Department of Molecular Biology and Biochemistry,6 Osaka University Graduate School of Medicine/Faculty of Medicine, Suite 565-0871, Osaka, Japan
The members of the nectin/CD155 gene family represent a growing class of novel cell adhesion molecules of the immunoglobulin superfamily. In the present study, we describe the generation of a mouse line lacking a functional nectin-2 gene (nectin-2LacZ/LacZ) and analyze the resulting male-specific infertility phenotype. Although nectin-2LacZ/LacZ males produced normal amounts of motile spermatozoa, scanning electron microscopy revealed severe malformations of the spermatozoan head and midpiece. Besides a 4-fold reduction in migration of nectin-2LacZ/LacZ spermatozoa to the oviducts, in vitro binding to zona-intact mouse oocytes was reduced 6-fold. On the other hand, nectin-2LacZ/LacZ spermatozoa bound to zona-free hamster oocytes at near-wild type levels but, remarkably, failed to penetrate. In addition to the previously reported expression of nectin-2 and nectin-3 at Sertoli-spermatid junctions and of nectin-2 at inter-Sertoli cell junctions, we also found nectin-2 to localize at apical cell-cell junctions of the epididymal epithelium. Expression analysis of a LacZ knockin gene into the defunct nectin-2 gene in nectin-2LacZ/LacZ mice provided additional support for our earlier conjecture that in normal testis, nectin-2 is produced exclusively by Sertoli cells. Finally, we found Sertoli-spermatid junctions in nectin-2LacZ/LacZ mice to be virtually devoid of the actin-bundling protein espin, suggesting that ectoplasmic specializations fail to form in the absence of nectin-2. Our functional analyses indicate that the infertility phenotype of nectin-2-deficient male mice is caused by a combination of reduced migration to the oviduct, spermatozoa-zona binding, and sperm-oocyte fusion. We corroborate our previous description of a heterotypic adhesion complex between Sertoli cells and elongated spermatids that is maintained by nectin-2 and nectin-3, respectively.
2 Correspondence: Eckard Wimmer, Department of Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794. FAX: 631 632 8891; ewimmer{at}ms.cc.sunysb.edu
This article has been cited by other articles:
|
|
 |
|
  D. D. Mruk, B. Silvestrini, and C. Y. Cheng Anchoring Junctions As Drug Targets: Role in Contraceptive Development Pharmacol. Rev., June 1, 2008; 60(2): 146 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Fujita, Y. Tanabe, T. Hirose, M. Aurrand-Lions, T. Kasahara, B. A. Imhof, S. Ohno, and T. Momoi Loss of Partitioning-Defective-3/Isotype-Specific Interacting Protein (Par-3/ASIP) in the Elongating Spermatid of RA175 (IGSF4A/SynCAM)-Deficient Mice Am. J. Pathol., December 1, 2007; 171(6): 1800 - 1810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Bronson, S. K. Bronson, and L. D. Oula Ability of Abnormally-Shaped Human Spermatozoa to Adhere to and Penetrate Zona-Free Hamster Eggs: Correlation With Sperm Morphology and Postincubation Motility J Androl, September 1, 2007; 28(5): 698 - 705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Q.F. Wang and C. Y. Cheng A seamless trespass: germ cell migration across the seminiferous epithelium during spermatogenesis J. Cell Biol., August 9, 2007; 178(4): 549 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wakamatsu, H. Ogita, N. Okabe, K. Irie, M. Tanaka-Okamoto, H. Ishizaki, A. Ishida-Yamamoto, H. Iizuka, J. Miyoshi, and Y. Takai Up-regulation of Loricrin Expression by Cell Adhesion Molecule Nectin-1 through Rap1-ERK Signaling in Keratinocytes J. Biol. Chem., June 22, 2007; 282(25): 18173 - 18181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goossens, B. Janssens, G. Vanpoucke, R. De Rycke, J. van Hengel, and F. van Roy Truncated isoform of mouse {alpha}T-catenin is testis-restricted in expression and function FASEB J, March 1, 2007; 21(3): 647 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Surace, A. Strickland, R. A. Hess, D. H. Gutmann, and C. K. Naughton Tslc1 (Nectin-Like Molecule-2) Is Essential for Spermatozoa Motility and Male Fertility J Androl, November 1, 2006; 27(6): 816 - 825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Inagaki, K. Irie, H. Ishizaki, M. Tanaka-Okamoto, J. Miyoshi, and Y. Takai Role of cell adhesion molecule nectin-3 in spermatid development. Genes Cells, September 1, 2006; 11(9): 1125 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. van der Weyden, M. J. Arends, O. E. Chausiaux, P. J. Ellis, U. C. Lange, M. A. Surani, N. Affara, Y. Murakami, D. J. Adams, and A. Bradley Loss of TSLC1 Causes Male Infertility Due to a Defect at the Spermatid Stage of Spermatogenesis. Mol. Cell. Biol., May 1, 2006; 26(9): 3595 - 3609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Fujita, Y. Kouroku, S. Ozeki, Y. Tanabe, Y. Toyama, M. Maekawa, N. Kojima, H. Senoo, K. Toshimori, and T. Momoi Oligo-Astheno-Teratozoospermia in Mice Lacking RA175/TSLC1/SynCAM/IGSF4A, a Cell Adhesion Molecule in the Immunoglobulin Superfamily Mol. Cell. Biol., January 15, 2006; 26(2): 718 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Inagaki, K. Irie, H. Ishizaki, M. Tanaka-Okamoto, K. Morimoto, E. Inoue, T. Ohtsuka, J. Miyoshi, and Y. Takai Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body development Development, April 1, 2005; 132(7): 1525 - 1537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sato, Y. Kanai, T. Noma, M. Kanai-Azuma, S. Taya, T. Matsui, M. Ishii, H. Kawakami, M. Kurohmaru, K. Kaibuchi, et al. A close correlation in the expression patterns of Af-6 and Usp9x in Sertoli and granulosa cells of mouse testis and ovary Reproduction, November 1, 2004; 128(5): 583 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Neubauer, K. Jewgenow, S. Blottner, D. E. Wildt, and B. S. Pukazhenthi Quantity Rather Than Quality in Teratospermic Males: A Histomorphometric and Flow Cytometric Evaluation of Spermatogenesis in the Domestic Cat (Felis catus) Biol Reprod, November 1, 2004; 71(5): 1517 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Guttman, Y. Takai, and A. W. Vogl Evidence That Tubulobulbar Complexes in the Seminiferous Epithelium Are Involved with Internalization of Adhesion Junctions Biol Reprod, August 1, 2004; 71(2): 548 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P.Y. Lee and C. Y. Cheng Ectoplasmic specialization, a testis-specific cell-cell actin-based adherens junction type: is this a potential target for male contraceptive development? Hum. Reprod. Update, July 1, 2004; 10(4): 349 - 369. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
