Lack of Delta-Sarcoglycan (Sgcd) Results in Retinal Degeneration

Abstract

Age-related macular degeneration (AMD) is the leading cause of central vision loss and severe blindness among the elderly population. Recently, we reported on the association of the SGCD gene (encoding for δ-sarcoglycan) polymorphisms with AMD. However, the functional consequence of Sgcd alterations in retinal degeneration is not known. Herein, we characterized changes in the retina of the Sgcd knocked-out mouse (KO, Sgcd−/−). At baseline, we analyzed the retina structure of three-month-old wild-type (WT, Sgcd+/+) and Sgcd−/− mice by hematoxylin and eosin (H&E) staining, assessed the Sgcd–protein complex (α-, β-, γ-, and ε-sarcoglycan, and sarcospan) by immunofluorescence (IF) and Western blot (WB), and performed electroretinography. Compared to the WT, Sgcd−/− mice are five times more likely to have retinal ruptures. Additionally, all the retinal layers are significantly thinner, more so in the inner plexiform layer (IPL). In addition, the number of nuclei in the KO versus the WT is ever so slightly increased. WT mice express Sgcd-protein partners in specific retinal layers, and as expected, KO mice have decreased or no protein expression, with a significant increase in the α subunit. At three months of age, there were no significant differences in the scotopic electroretinographic responses, regarding both a- and b-waves. According to our data, Sgcd−/− has a phenotype that is compatible with retinal degeneration.

The sockeye salmon genome, transcriptome, and analyses identifying population defining regions of the genome

“…an association identified in the analysis between all sockeye and kokanee), is a component of the sarcoglycan subcomplex that stabilizes skeletal muscle fiber sheaths among other functions (reviewed in [ 135 ]). Variants of this gene are associated with muscular dystrophy in humans [ 136 ], and this gene plays a role in the longevity of the retina in mice [ 137 ]. The sacrospan gene, another candidate gene, associates with the sarcoglycan subcomplex [ 138 ].…”

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

“…The biological mechanisms associated with several of the protein products of identified genes have been linked to PTSD pathophysiology in animal and cell models: amygdala-mediated fear extinction [FAM120A ( 38 )], neuronal transcriptional regulation [FOXP2 ( 39 )], brain excitatory/inhibitory balance [ARFGEF2, GABBR1, STAUI1 ( 40 )], intracellular vesicular trafficking and other synaptic activities [ARFGEF2 ( 41 ), MPP6 ( 42 ), SEMA6C ( 43 ), SGCD ( 44 )], and inflammation [HIATL1, TRIM26 ( 45 ), TRIM27 ( 46 ), ZMYM4, ZNF165 ( 47 )]. Blood and brain transcription-wide association and differential gene expression studies of PTSD have also implicated some of these genes, including a blood-based prediction of downregulation of ARFGEF2 in the dorsolateral prefrontal cortex ( 48 ) and a postmortem study of human PTSD cortex indicating downregulation of CTSS expression in the dorsal anterior cingulate cortex and downregulation of OSBPL3 expression in the dorsolateral prefrontal cortex ( 49 ).…”