Ccdc66 null mutation causes retinal degeneration and dysfunction

Gerding WM, Schreiber S, Schulte-Middelmann T, Marques ADC, Atorf J, Akkad DA, Dekomien G, Kremers J, Dermietzel R, Gal A, Ruelicke T, Ibrahim S, Epplen JT, Petrasch-Parwez E (2011)

Publication Type: Journal article

Publication year: 2011

Journal

Human Molecular Genetics Oxford University Press (OUP): Policy B - Oxford Open Option B

Book Volume: 20

Pages Range: 3620-31

Journal Issue: 18

DOI: 10.1093/hmg/ddr282

Abstract

Retinitis pigmentosa (RP) is a group of human retinal disorders, with more than 100 genes involved in retinal degeneration. Canine and murine models are useful for investigating human RP based on known, naturally occurring mutations. In Schapendoes dogs, for example, a mutation in the CCDC66 gene has been shown to cause autosomal recessively inherited, generalized progressive retinal atrophy (gPRA), the canine counterpart to RP. Here, a novel mouse model with a disrupted Ccdc66 gene was investigated to reveal the function of protein CCDC66 and the pathogenesis of this form of gPRA. Homozygous Ccdc66 mutant mice lack retinal Ccdc66 RNA and protein expression. Light and electron microscopy reveal an initial degeneration of photoreceptors already at 13 days of age, followed by a slow, progressive retinal degeneration over months. Retinal dysfunction causes reduced scotopic a-wave amplitudes, declining from 1 to 7 months of age as well as an early reduction of the photopic b-wave at 1 month, improving slightly at 7 months, as evidenced by electroretinography. In the retina of the wild-type (WT) mouse, protein CCDC66 is present at highest levels after birth, followed by a decline until adulthood, suggesting a crucial role in early development. Protein CCDC66 is expressed predominantly in the developing rod outer segments as confirmed by subcellular analyses. These findings illustrate that the lack of protein CCDC66 causes early, slow progressive rod-cone dysplasia in the novel Ccdc66 mutant mouse model, thus providing a sound foundation for the development of therapeutic strategies.

Authors with CRIS profile

Jenny Atorf Department of Ophthalmology Jan Kremers Professur für Experimentelle Augenheilkunde

Involved external institutions

Ruhr-Universität Bochum (RUB) DE Germany (DE) Stiftung Tierärztliche Hochschule Hannover (TiHo) DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universität zu Lübeck DE Germany (DE)

How to cite

APA:

Gerding, W.M., Schreiber, S., Schulte-Middelmann, T., Marques, A.D.C., Atorf, J., Akkad, D.A.,... Petrasch-Parwez, E. (2011). Ccdc66 null mutation causes retinal degeneration and dysfunction. Human Molecular Genetics, 20(18), 3620-31. https://doi.org/10.1093/hmg/ddr282

MLA:

Gerding, Wanda M., et al. "Ccdc66 null mutation causes retinal degeneration and dysfunction." Human Molecular Genetics 20.18 (2011): 3620-31.

BibTeX: Download