Sarcospan-deficient mice maintain normal muscle function

Sarcospan is an integral membrane component of the dystrophin-glycoprotein complex (DGC) found at the sarcolemma of striated and smooth muscle. The DG C plays important roles in muscle function and viability as evidenced by de fects in components of the DGC, which cause muscular dystrophy. Sarcospan i s unique among the components of the complex in that it contains four trans membrane domains with intracellular Nand C-terminal domains and is a member of the tetraspan superfamily of proteins. Sarcospan is tightly linked to t he sarcoglycans, and together these proteins form a subcomplex within the D GC. Stable expression of sarcospan at the sarcolemma is dependent upon expr ession of the sarcoglycans. Here we describe the generation and analysis of mice carrying a null mutation in the Sspn gene. Surprisingly, the Sspn-def icient muscle maintains expression of other components of the DGC at the sa rcolemma, and no gross histological abnormalities of muscle from the mice a re observed. The Sspn-deficient muscle maintains sarcolemmal integrity as d etermined by serum creatine kinase and Evans blue uptake assays, and the Ss pn-deficient muscle maintains normal force and power generation capabilitie s. These data suggest either that sarcospan is not required for normal DGC function or that the Sspn-deficient muscle is compensating for the absence of sarcospan, perhaps by utilizing another protein to carry out its functio n.