alpha 1-syntrophin gene disruption results in the absence of neuronal-typenitric-oxide synthase at the sarcolemma but does not induce muscle degeneration

alpha 1-Syntrophin is a member of the family of dystrophin-associated prote ins and is strongly expressed in the sarcolemma and the neuromuscalar junct ions. All three syntrophin isoforms have a PDZ domain that appears to parti cipate in protein-protein interactions at the plasma membrane. alpha 1-Synt rophin has additionally been shown to associate with neuronal nitric-oxide synthase (nNOS) through PDZ domains in vitro. These observations suggest th at alpha 1-syntrophin may work as a modular adaptor protein that can link n NOS or other signaling enzyme to the sarcolemmal dystrophin complex. In the sarcolemma, nNOS regulates the homeostasis of reactive free radical specie s and may contribute to the oxidative damage to muscle protein in muscle di sease such as Duchenne muscular dystrophy. In this study, we generated alph a 1-syntrophin knockout mice to clarify the interaction between alpha 1-syn trophin and nNOS in the skeletal muscle. We observed that nNOS, normally ex pressed in the sarcolemma, was largely absent from the sarcolemma, but cons iderably remained in the cytosol of the knock-out mice. Even though the dis tribution of nNOS was altered, the knock-out mice displayed no gross histol ogical changes in the skeletal muscle. We also discovered that muscle contr actile properties have not been influenced in the knock-out mice.