Business address

Molecular Genetics Laboratory
Institute for Ophthalmic Research
Centre for Ophthalmology,
University of Tübingen
Elfriede-Aulhorn-Strasse 7
D-72076 Tübingen,
Germany

Phone: +49 (0)7071 29-80704
Fax: +49 (0)7071 29-5725
E-mail: peggy.reuter[at]med.uni-tuebingen.de

Cone cyclic nucleotide-gated (CNG) channels are non-selective cation channels, which possess – as part of the phototransduction cascade – a crucial function in the detection of light via the rod and cone photoreceptors. Through an enzymatic cascade, light can trigger the intracellular cGMP level and thus mediate the opening and closure of the CNG channels. Consequently, the influx of sodium and calcium ions through the channels into the photoreceptor outer segment is regulated.

Cone CNG channels are heterooligomers consisting of one CNGB3 - and three CNGA3-subunits, which are encoded by the CNGB3 and the CNGA3 gene. In both genes, mutations have been identified which can lead to a dysfunction of the CNG channels in cone photoreceptors. In humans this results in the disease achromatopsia (color blindness), a congenital, autosomal recessively inherited retinal disorder characterized by lack of color discrimination, reduced visual acuity, nystagmus and photophobia.

My project aims on the establishment of zebrafish as an animal model for achromatopsia to gain a deeper insight into cone photoreceptor physiology and to clarify how the presence of mutant CNG channels affect and impair cone function.

1. Koeppen K, Reuter P, Kohl S, Baumann B, Ladewig T, Wissinger B. Functional analysis of human CNGA3 mutations associated with colour blindness suggests impaired surface expression of channel mutants A3(R427C) and A3(R563C). Eur J Neurosci. 2008 May;27(9):2391-2401.
2. Reuter P*, Koeppen K*, Ladewig T, Kohl S, Baumann B, Wissinger B; Achromatopsia Clinical Study Group. Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia. Hum Mutat. 2008 Oct; 29(10):1228-36. * Both authors contributed equally to this work
3. Koeppen K*, Reuter P*, Ladewig T, Kohl S, Baumann B, Jacobson SG, Plomp AS, Hamel CP, Janecke AR, Wissinger B. Dissecting the pathogenic mechanisms of mutations in the pore region of the human cone photoreceptor cyclic nucleotide-gated channel. Hum Mutat. 2010 Jul;31(7):830-9. * Both authors contributed equally to this work