IOVS Read the Free BMJ
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2004;45:2767-2777.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-0020
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (14)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rice, D. S.
Right arrow Articles by Sands, A. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rice, D. S.
Right arrow Articles by Sands, A. T.

Severe Retinal Degeneration Associated with Disruption of Semaphorin 4A

Dennis S. Rice,1 Wenhu Huang,1 Holly A. Jones,1 Gwenn Hansen,1 Gui-Lan Ye,1 Nianha Xu,1 Elizabeth A. Wilson,1 Kathy Troughton,2 Kris Vaddi,3 Robert C. Newton,3 Brian P. Zambrowicz,1 and Arthur T. Sands1

1From Lexicon Genetics Inc., The Woodlands, Texas; the 2Department of Anatomy and Neurobiology, The University of Tennessee, Memphis, Tennessee; and 3Incyte Corporation, Experimental Station, Wilmington, Delaware.

PURPOSE. Semaphorin 4A (Sema4A) is a member of the transmembrane class 4 family of semaphorins. It has recently been shown to participate in cell–cell communication in the immune system. High levels of sema4A are also present in brain and eye, but its function in the central nervous system has not been studied. To investigate the function of Sema4A, we generated mice deficient in this transmembrane signaling molecule.

METHODS. An embryonic stem (ES) cell clone with a retroviral gene-trap insertion in the sema4A gene was used to generate mice lacking this transmembrane semaphorin. Fundus photography, fluorescein angiography, and electroretinography were used to evaluate retinal anatomy and physiology in mice lacking Sema4A. Electron microscopy and immunohistochemistry with cell-type–specific markers were used to characterize retinal development. In situ hybridization with sema4A-specific riboprobes was used to localize expression of this gene in the developing and adult eye.

RESULTS. Fundus photography performed at 14 weeks of age revealed severe retinal degeneration, attenuated retinal vessels, and depigmentation in mice lacking Sema4A. At this age, the outer nuclear layer was reduced to a single row of photoreceptor cells, and the outer plexiform layer was thin and disorganized. Disruption of Sema4A also compromised the physiological function of both rod and cone photoreceptors. Developmental studies in Sema4A-deficient mice revealed abnormal morphology of photoreceptor outer segments during the time at which they establish contacts with apical microvilli of the retinal pigment epithelium (RPE). Sema4A is expressed in the inner retina and RPE during the time at which photoreceptor outer segments elongate.

CONCLUSIONS. These findings identify a previously unknown function of Sema4A in the developing visual system and provide a useful model for understanding cell–cell interactions that occur between photoreceptors and the RPE.




This article has been cited by other articles:


Home page
 Genome ResHome page
G. M. Hansen, D. C. Markesich, M. B. Burnett, Q. Zhu, K. M. Dionne, L. J. Richter, R. H. Finnell, A. T. Sands, B. P. Zambrowicz, and A. Abuin
Large-scale gene trapping in C57BL/6N mouse embryonic stem cells
Genome Res., October 1, 2008; 18(10): 1670 - 1679.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
C. M. Gelfman, P. Vogel, T. M. Issa, C. A. Turner, W.-S. Lee, S. Kornfeld, and D. S. Rice
Mice Lacking {alpha}/{beta} Subunits of GlcNAc-1-Phosphotransferase Exhibit Growth Retardation, Retinal Degeneration, and Secretory Cell Lesions
Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5221 - 5228.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. Schmidt, K. Paes, A. De Maziere, T. Smyczek, S. Yang, A. Gray, D. French, I. Kasman, J. Klumperman, D. S. Rice, et al.
EGFL7 regulates the collective migration of endothelial cells by restricting their spatial distribution
Development, August 15, 2007; 134(16): 2913 - 2923.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
S. M. Rollmann, A. Yamamoto, T. Goossens, L. Zwarts, Z. Callaerts-Vegh, P. Callaerts, K. Norga, T. F. C. Mackay, and R. R. H. Anholt
The Early Developmental Gene Semaphorin 5c Contributes to Olfactory Behavior in Adult Drosophila
Genetics, June 1, 2007; 176(2): 947 - 956.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. M. Ogilvie, K. K. Ohlemiller, G. N. Shah, B. Ulmasov, T. A. Becker, A. Waheed, A. K. Hennig, P. D. Lukasiewicz, and W. S. Sly
Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response
PNAS, May 15, 2007; 104(20): 8514 - 8519.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
A Abid, M Ismail, S Q Mehdi, and S Khaliq
Identification of novel mutations in the SEMA4A gene associated with retinal degenerative diseases
J. Med. Genet., April 1, 2006; 43(4): 378 - 381.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2004 by the Association for Research in Vision and Ophthalmology