Purchase this article with an account.
Venkata R. Chavali, Bhubanananda Sahu, Dirk-Uwe Bartsch, Tarun Bansal, Christine A. Curcio, Sheldon S. Miller, Monica M. Jablonski, Radha Ayyagari; Absence Of Ctrp5/c1qtnf5 Leads To RPE Degeneration In Ctrp5 Gene Knock-out Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):308.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Autosomal dominant late-onset retinal degeneration (L-ORD) in humans is caused by a S163R mutation in the C1QTNF5/CTRP5 gene. To study the function of this gene and to understand the molecular pathology of L-ORD, a Ctrp5 gene knock-out mouse model (Ctrp5-/-) was generated and its retinal phenotype was characterized.
The Ctrp5-/- mice were generated on a C57BL/6 background. The homozygous knock-out mice were characterized by examining the Ctrp5 gene transcript and protein by RT-PCR and western blot analysis. Retinal pathology was evaluated by fundus photography, fundus autofluorescence (FAF) imaging, fluorescein angiography (FA), Optical coherence tomography (OCT), dc-electroretinography (dc-ERG). Retinal morphology was evaluated by light and electron microscopy; immunohistochemistry with retinal and RPE marker antibodies and staining for lipids. Expression levels of retinal and RPE cell marker genes were determined by qRT-PCR. All assays were done through age 8 months and some assays up to 18 mo.
The Ctrp5 transcript and protein were not detected in the homozygous knock-out mice. Fundus examination revealed increased accumulation of hyperfluorescent spots in Ctrp5-/- mice from age 5 months compared to littermate controls. Morphological analysis revealed abnormalities in the RPE and in the outer segments (OS). The RPE developed many vacuoles and appeared to be necrotic. The underlying photoreceptor OS below the necrotic RPE appeared shorter and disorganized along with presence of swollen inner segments (IS). The sub-retinal space consisted of debris that appeared to contain undigested packets of OS, melanin granules and other material of unknown origin. These morphological changes were found to be progressive with age. The Ctrp5-/- mice had little or no basal laminar deposits, compared to what we previously observed in Ctrp5 S163R knock-in mice. In addition, expression levels of photoreceptor marker genes were significantly reduced with age in the Ctrp5-/- mice, compared to the wild type littermate controls. The dc-ERG response was significantly reduced in the Ctrp5-/- mice by 8 months.
The homozygous Ctrp5 gene knock-out mice developed RPE and photoreceptor degeneration. This model is complementary to the Ctrp5 S163R knock-in model previously developed in the lab and will also help elucidate the molecular pathology of L-ORD.
This PDF is available to Subscribers Only