PMID:21680557

Citation	Gerding, WM, Schreiber, S, Schulte-Middelmann, T, de Castro Marques, A, Atorf, J, Akkad, DA, Dekomien, G, Kremers, J, Dermietzel, R, Gal, A, Rülicke, T, Ibrahim, S, Epplen, JT and Petrasch-Parwez, E (2011) Ccdc66 null mutation causes retinal degeneration and dysfunction. Hum. Mol. Genet. 20:3620-31
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.
Links	PubMed Online version:10.1093/hmg/ddr282
Keywords	Animals; Disease Models, Animal; Eye Proteins/genetics; Female; Gene Silencing; Humans; Male; Mice; Mice, Knockout; Retina/metabolism; Retina/pathology; Retina/physiopathology; Retinal Degeneration/genetics; Retinal Degeneration/metabolism; Retinal Degeneration/pathology; Retinal Degeneration/physiopathology; Retinitis Pigmentosa/genetics; Retinitis Pigmentosa/metabolism; Retinitis Pigmentosa/pathology; Retinitis Pigmentosa/physiopathology; Sequence Deletion
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:CCD66		GO:0050908: detection of light stimulus involved in visual perception	ECO:0000315:		P		Figure 3: Ccdc66 -/- mouse at 3 months revealed a reduced a-wave amplitude under scotopic conditions and a reduced b-wave amplitude under photopic conditions on a background intensity of 25 cd/m^2.	complete CACAO 4362
MOUSE:CCD66	acts_upstream_of_or_within	GO:0046548: retinal rod cell development	ECO:0000315: mutant phenotype evidence used in manual assertion	MGI:MGI:3893603	P	occurs_in:(EMAPA:35688) results_in_development_of:(CL:0000604)	Seeded From UniProt	complete
MOUSE:CCD66	acts_upstream_of_or_within	GO:0060060: post-embryonic retina morphogenesis in camera-type eye	ECO:0000315: mutant phenotype evidence used in manual assertion	MGI:MGI:3893603	P	has_participant:(EMAPA:35688)	Seeded From UniProt	complete
MOUSE:CCD66	involved_in	GO:0050908: detection of light stimulus involved in visual perception	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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