IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2006;47:3523-3530.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-0271
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
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 (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wycisk, K. A.
Right arrow Articles by Berger, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wycisk, K. A.
Right arrow Articles by Berger, W.

Structural and Functional Abnormalities of Retinal Ribbon Synapses due to Cacna2d4 Mutation

Katharina A. Wycisk,1 Birgit Budde,2,3 Silke Feil,1,3 Sergej Skosyrski,4 Francesca Buzzi,1 John Neidhardt,1 Esther Glaus,1 Peter Nürnberg,2 Klaus Ruether,4 and Wolfgang Berger1

1From the Division of Medical Molecular Genetics and Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland; the 2Cologne Centre for Genomics and Institute for Genetics, University of Cologne, Cologne, Germany; and the 4Charite-Virchow-Augenklinik, Berlin, Germany.

PURPOSE. In a spontaneous mutant substrain of C57BL/10 mice, severely affected retinal ribbon-type synapses have been described. The retinopathy was accompanied by a substantial loss in the activities of the second-order neurons. Rod photoreceptor responses were maintained with reduced amplitude, whereas cone activities were absent. This study was conducted to identify the genetic defect underlying this hitherto unknown autosomal recessive cone–rod dysfunction.

METHODS. Genome-wide linkage analysis and screening of positional candidate genes were used to identify the causative mutation. Tissue-specific transcriptional activity of the defective gene was determined by Northern blot analysis and RT-PCR approaches. The number of cone photoreceptors was estimated by immunohistochemistry.

RESULTS. The mutation was localized to a 275-kb region of chromosome 6. Within this candidate interval, a homozygous frameshift mutation (c.2367insC) was identified in the Cacna2d4 gene of affected animals. This gene codes for an L-type calcium channel auxiliary subunit of the {alpha}2{delta} type. The mutation introduces a premature stop codon that truncates one third of the predicted Cacna2d4 protein. A severe reduction in Cacna2d4 transcript levels observed in mutant retinas probably results in the lack of Cacna2d4 protein. The mutation leads to significant loss of rods, whereas the number of cone cells remains unaffected until 6 weeks of age.

CONCLUSIONS. The Cacna2d4 mutation underlies a novel channelopathy leading to cone–rod dysfunction in the visual system of mice and provides a new candidate gene for human retinal disorders including night blindness, retinitis pigmentosa, and cone–rod dystrophies.




This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
N. Axelrod, Y. Lin, P. C. Ng, T. B. Stockwell, J. Crabtree, J. Huang, E. Kirkness, R. L. Strausberg, M. E. Frazier, J. C. Venter, et al.
The HuRef Browser: a web resource for individual human genomics
Nucleic Acids Res., January 1, 2009; 37(suppl_1): D1018 - D1024.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
M. A. McCall and R. G. Gregg
Comparisons of structural and functional abnormalities in mouse b-wave mutants
J. Physiol., September 15, 2008; 586(18): 4385 - 4392.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
C. V. Ly, C.-K. Yao, P. Verstreken, T. Ohyama, and H. J. Bellen
straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel {alpha}1 subunit
J. Cell Biol., April 3, 2008; 181(1): 157 - 170.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
D. K. Dickman, P. T. Kurshan, and T. L. Schwarz
Mutations in a Drosophila {alpha}2{delta} Voltage-Gated Calcium Channel Subunit Reveal a Crucial Synaptic Function
J. Neurosci., January 2, 2008; 28(1): 31 - 38.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. Yang, B. Pawlyk, X.-H. Wen, M. Adamian, M. Soloviev, N. Michaud, Y. Zhao, M. A. Sandberg, C. L. Makino, and T. Li
Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals
Hum. Mol. Genet., May 1, 2007; 16(9): 1017 - 1029.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2006 by the Association for Research in Vision and Ophthalmology