Skip to main content

17-07-2011 | Genetics | Article

CCDC66 protein implicated in development of retinitis pigmentosa


Free abstract

MedWire News: Investigation of a novel mouse model for the study of retinitis pigmentosa (RP) shows that lack of the coiled-coil domain-containing 66 gene (CCDC66) results in slow progressive rod-cone dysplasia.

"The slow, progressive degeneration described [in our study] appears particularly advantageous for retinal investigations, because it reflects a typical course for RP in humans," say Wanda Gerding (Ruhr University, Bochum, Germany) and co-authors.

To investigate the functional aspects of CCDC66, the team developed a mouse model with a constitutive Ccdc66 null mutation. The expression of CCDC66 was then investigated during postnatal development, and its subcellular localization in mouse photoreceptors analyzed.

Light and electron microscopy revealed initial photoreceptor degeneration at 13 days of age, followed by a slow, progressive retinal phenotype and physiologic impairment of the retina.

Conversely, wild-type mice showed a high level of CCDC66 protein after birth, followed a slow decline until adulthood. The researchers say this particular difference in deterioration suggests a crucial role of CCDC66 in early development.

Gerding and team also found that the CCDC66 protein was expressed predominantly in the developing rod outer segments, correlating with photoreceptor degeneration seen around the eye opening.

When the researchers assessed functional integrity of retinal structures using electroretinography, they found an advanced degeneration of photoreceptors in mutant mice at age 1, 3, and 7 months, which manifested itself as a progressive age-related reduction in scotopic a-wave amplitude.

Furthermore, the authors observed a reduction in photopic b-wave amplitude at 1 and 3 months, which improved to levels seen in wild-type mice at 7 months of age.

Cone photoreceptor functionality remained in knockout mice, despite severe degeneration of rod photoreceptors, suggesting that combined rod-cone retinopathy occurs predominantly in the rod photoreceptors.

"Based on canine and mouse data, CCDC66 dysfunction induces retinal degeneration, following autosomal recessive inheritance. Thus, in the future, patients with unknown causes of retinal degeneration will be investigated," say the authors in the journal Human Molecular Genetics.

Gerding said the mouse model will be studied further, "with regard to malfunctions of the brain, but naturally, above all as a pre-requisite for future therapeutic trial in retinitis pigmentosa."

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Ingrid Grasmo

Related topics