Myasthenia+Gravis

Jennifer Ledoux Jbm5@wildcats.unh.edu Myasthenia Gravis (MG) is a chronic autoimmune neuromuscular disorder that is characterized by weakness of the voluntary muscle groups (Tuzun, Erdem et al., 2011). MG is not thought to be directly inherited but does occasionally occur in more than one member of the same family.

The voluntary muscles of the entire body are controlled by nerve impulses from the brain. The impulses travel down the nerves to meet the muscle fibers. Nerve fibers and muscle fibers do not physically join. The space between the nerve ending and muscle fiber is called the neuromuscular junction.

Once the brain triggered nerve impulse gets to the nerve ending, it releases a chemical called acetylcholine. Acetylcholine (ACh) travels across the space of the neuromuscular junction (NMJ) where it attaches to many receptor sites of the muscle fiber. The muscle responds when enough of the receptors have been activated by the acetylcholine.

Myasthenia Gravis patients are not able to receive the acetylcholine due to an immune response from the body. Normally, to fight off bacteria and viruses, proteins called antibodies get released to kill these foreign objects (antigens). Instead, the antibodies that are supposed to defend, attack or block the receptor sites at the NMJ of Myasthenia Gravis patients. Since the muscles cannot respond to ACh, muscle contraction cannot occur. If the muscles aren’t used, they become weakened. In addition to chronic weakness, MG sufferers tend to have other symptoms such as drooping eyelids, blurred vision, slurred speech, and difficulty breathing.

There are two interesting components of the NMJ that work hand in hand. The first is the acetylcholine receptor site protein (AChR). AChR is needed to cluster on the muscle membrane to make it move (Pal, Jozsef et al., 2010). This clustering can only happen when a protein called rapsyn is present. Rapsyn binds to the part of muscle fibers called actin (Jozsef. Pal et al., 2010). Actin is responsible for the fiber to tighten making the muscle shorter and the attached body part move. The second component is another receptor protein called the muscle-specific receptor kinase (MuSK). This protein works with another one referred to Lrp4. When these become activated or active, they mix with other proteins agrin and Dok7. They all come together to create the clustering of rapsyn (Pal, Jozsef et al., 2010). Without rapsyn being produced from MuSK, AChR would not be able to bind to the activation site within the NMJ.



Myasthenia gravis patients have some kind of problem within this area and with these different proteins. It has not been proven yet, which ones specifically cause all of the above symptoms. There have been many studies and trials to determine which ones are either missing or mutated.

Genomics question to research: “What gene contributes to the NMJ and its attack on the immune system?

MG Gene of Interest -> MG Diagnosis and Treatment-> Genomic and Bioinformatic Tools -> MG References 

 Myasthenia Gravis Jennifer Ledoux Jbm5@wildcats.unh.edu  MG Diagnosis and Treatment MG Diagnosis and Treatment