A mouse model for studying cone photoreceptor pathologies

Marijana Samardzija, Christian Caprara, Severin R. Heynen, Sarah Willcox DeParis, Isabelle Meneau, Ghislaine Traber, Cavit Agca, Johannes von Lintig, Christian Grimm

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Purpose. Due to the low abundance of cone photoreceptors in the mouse retina and the scarcity of alternative animal models, little is known about mechanisms of cone degeneration. Nrl knockout mice develop exclusively the cone-type of photoreceptors. However, the cone photoreceptor layer in Nrl-/- mice displays an irregular morphology with severe rosette formation. Retinas of Rpe65-/-;Nrl-/- mice have no rosettes due to the lack of 11-cis-retinal, but also are not functional. To develop a model with a functional all-cone retina that is morphologically well structured, we generated R91W;Nrl-/- double-mutant mice, which express a hypomorphic Rpe65 allele (R91W). Methods. The following analyses were used to characterize the R91W;Nrl-/-mice: morphology by light and electron microscopy, protein distribution by immunofluorescence, cone function by electroretinography and optomotor response, RNA levels by RT-PCR, and chromophore levels by HPLC. Cone degeneration was assessed in R91W;Nrl-/- mice treated with MNU, and in tripleR91W;Nrl-/-;Cpfl1 and quadruple R91W;Nrl-/-;Cpfl1;rd10 mutant mice. Results. The all-cone retina of R91W;Nrl-/- mice is functional and relatively stable with only very slow age-related degeneration. Using triple and quadruple mutant mice, or a chemical treatment, we demonstrated that cone degeneration could be induced and analyzed in these mice. Conclusions. The reduced levels of visual chromophore prevented rosette formation and sustained function in the R91W;Nrl-/- retina. Thus, the R91W;Nrl-/- mouse allows study of the etiology of diseases related to cone degeneration in a "morphologically intact" and functional all-cone photoreceptor retina.

Original languageEnglish (US)
Pages (from-to)5304-5313
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Issue number8
StatePublished - Jul 17 2014


  • AMD
  • Cone cell death
  • Mouse model
  • RPE65

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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