Disease relevance of Sgcd

• We found that only Sgcd null mice developed cardiomyopathy with focal areas of necrosis as the histological hallmark in cardiac and skeletal muscle [1].
• A defect in any one of the four SG members disrupts the entire SG complex (SGC) and causes limb-girdle muscular dystrophy. zeta-SG has been recently found as a transmembrane protein homologous to gamma-SG and delta-SG [2].
• Recessive mutations of delta-sarcoglycan that eliminate expression, and therefore function, lead to cardiomyopathy and muscular dystrophy by producing instability of the plasma membrane [3].
• Similar to the human delta-sarcoglycan gene mutation, S151A delta-sarcoglycan transgenic mice developed dilated cardiomyopathy at a young age with enhanced lethality [3].
• In the cardiomyopathic hamster, the smooth muscle sarcoglycan complex, containing epsilon-sarcoglycan, was fully restored following intramuscular injection of recombinant delta-sarcoglycan adenovirus [4].

High impact information on Sgcd

• Loss of vascular smooth muscle SG-SSPN complex was only detected in Sgcd null mice and associated with irregularities of the coronary vasculature [1].
• Cardiomyopathy in mice lacking gamma-sarcoglycan or delta-sarcoglycan is characterized by focal damage [5].
• The study demonstrates that wild-type bone marrow-derived side population stem cells are indeed readily incorporated into both skeletal and cardiac muscle when transplanted into mice that lack delta-sarcoglycan -- a model of cardiomyopathy and muscular dystrophy [6].
• The absence of delta-sarcoglycan produces microinfarcts in heart and skeletal muscle that should recruit regenerative stem cells [7].
• Here, we observed that the growth factor-regulated channel (GRC), which belongs to the transient receptor potential channel family, is elevated in the sarcolemma of skeletal and/or cardiac muscle in dystrophic human patients and animal models deficient in dystrophin or delta-sarcoglycan [8].

Chemical compound and disease context of Sgcd

• To explore the possibility that elevating alpha7beta1 integrin expression could also ameliorate different forms of muscular dystrophy, we used transgenic technology to enhance integrin expression in mice lacking delta-sarcoglycan (delta sgc), a mouse model for human limb girdle muscular dystrophy type 2F [9].

Biological context of Sgcd

• A dominant missense mutation in the gene encoding delta-sarcoglycan was previously shown to associate with dilated cardiomyopathy in humans [3].
• In this study, we report the identification of a novel isoform of murine delta-SG produced by alternative splicing that we named delta-SG3 [10].

Anatomical context of Sgcd

• In skeletal and cardiac muscle, sarcoglycans exist as a complex of four transmembrane proteins (alpha-, beta-, gamma-, and delta-SG) [11].
• We found that beta-SG appears to play an initiating role and its association with delta-SG is essential for the proper localization of the sarcoglycan complex to the cell membrane [11].
• This observation suggests that the epsilon-, beta- and delta-SG molecules form a complex behaving as a single unit similar to the SG complex in muscle cells [12].
• Analysis of the properties of myotubes prepared from delta-sarcoglycan-deficient BIO14.6 hamsters revealed that GRC is activated in response to myocyte stretch and is responsible for enhanced Ca2+ influx and resultant cell damage as measured by creatine phosphokinase efflux [8].
• By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that epsilon-sarcoglycan is an integral component of the smooth muscle sarcoglycan complex along with beta- and delta-sarcoglycan [4].

Associations of Sgcd with chemical compounds

• Furthermore, sucrose gradient ultracentrifugation demonstrated that delta-sarcoglycan was physically dissociated from dystrophin within the membrane fraction [13].

Other interactions of Sgcd

• The dystrophic hamster is a model of limb-girdle muscular dystrophy with sarcoglycan deficiency in which one of the dystrophin-associated glycoproteins, delta-sarcoglycan, is defective [14].
• Here we examined disease severity associated with myostatin (mstn-/-) deletion in mice nullizygous for delta-sarcoglycan (scgd-/-), a model of limb-girdle muscular dystrophy [15].

Analytical, diagnostic and therapeutic context of Sgcd

• Immunoelectron microscopy clarified that delta-sarcoglycan was localized in the terminal cisternae of the SR, while gamma-sarcoglycan was found in the terminal cisternae and longitudinal SR over I-bands but not over A-bands [16].
• Phase I clinical trial utilizing gene therapy for limb girdle muscular dystrophy: alpha-, beta-, gamma-, or delta-sarcoglycan gene delivered with intramuscular instillations of adeno-associated vectors [17].
• Skeletal myosphere-derived progenitor cell transplantation promotes neovascularization in delta-sarcoglycan knockdown cardiomyopathy [18].

References