The Usher gene cadherin 23 is expressed in the zebrafish brain and a subset of retinal amacrine cells

Mol Vis. 2012:18:2309-22. Epub 2012 Sep 5.

Abstract

Purpose: To characterize the expression pattern of cadherin 23 (cdh23) in the zebrafish visual system, and to determine whether zebrafish cdh23 mutants have retinal defects similar to those present in the human disease Usher syndrome 1D.

Methods: In situ hybridization and immunohistochemistry were used to characterize cdh23 expression in the zebrafish, and to evaluate cdh23 mutants for retinal degeneration. Visual function was assessed by measurement of the optokinetic response in cdh23 siblings and mutants.

Results: We detected cdh23 mRNA expression in multiple nuclei of both the developing and adult central nervous system. In the retina, cdh23 mRNA was expressed in a small subset of amacrine cells, beginning at 70 h postfertilization and continuing through adulthood. No expression was detected in photoreceptors. The cdh23-positive population of amacrine cells was GABAergic. Examination of homozygous larvae expressing two different mutant alleles of cdh23-cdh23(tc317e) or cdh23(tj264a)-revealed no detectable morphological retinal defects or degeneration. In addition, the optokinetic response to moving gratings of varied contrast or spatial frequency was normal in both mutants.

Conclusions: Unlike in other vertebrates, cdh23 is not detectable in zebrafish photoreceptors. Instead, cdh23 is expressed by a small subset of GABAergic amacrine cells. Moreover, larvae with mutations in cdh23 do not exhibit any signs of gross retinal degeneration or dysfunction. The role played by cdh23 in human retinal function is likely performed by either a different gene or an unidentified cdh23 splice variant in the retina that is not affected by the above mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Alternative Splicing
  • Amacrine Cells / cytology
  • Amacrine Cells / metabolism*
  • Animals
  • Cadherin Related Proteins
  • Cadherins / genetics*
  • Eye Movements
  • Gene Expression Regulation, Developmental*
  • Homozygote
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Larva / genetics*
  • Mutation*
  • Photoreceptor Cells / cytology
  • Photoreceptor Cells / metabolism
  • RNA, Messenger / biosynthesis
  • Receptors, GABA / genetics
  • Retinal Degeneration / genetics
  • Usher Syndromes / genetics
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics*

Substances

  • CDH23 protein, human
  • Cadherin Related Proteins
  • Cadherins
  • RNA, Messenger
  • Receptors, GABA
  • Zebrafish Proteins
  • cdh23 protein, zebrafish