Muscle Dystrophy

Before the motor neuron cone arrives the muscle fiber, AChR clusters are formed in the middle section of a muscle fiber. When the growing nerve cone attaches the muscle fiber, Agrin activates Lrp4, which then binds to the receptor tyrosine kinase MuSK, through this binding MuSK is phosphorylated and starts to form the neural and aneural AChR clustering (Burden 2011).
Morphologic differences in the pre- and/or postsynaptic part of the NMJ can be a hint of a certain disease. In the following figure, the structure differences between a wild type mouse and mdx mouse NMJ is compared. In research, an mdx mouse is used as a DMD animal model. Duchene muscular dystrophy (DMD) is a certain muscle disease caused by the absence of dystrophin that is found in the sarco-lemma. As it can be seen in Figure 2 the structure of the presynaptic part (green, staining of synaptophysin) and the postsynaptic part (red, staining of AChR) compared to the wild type NMJ, shows a fragmented structure. Due to this result, it can be said, that the protein dystophin is not necessary for the formation of a NMJ but it is necessary
Morphologic alteration like loss of connection between the nerve terminal and the muscle fiber could also be observed in older aged mice. The NMJ of a young and healthy mouse has normally a pretzel-shaped structure in the post- and presynaptic part of the NMJ, but in older mice, the structure could suddenly change and the pretzel-shaped structure remodels to fragmented AChR clusters (Cheng et al. 2013). The remodeling of the NMJ into fragmented nerve terminal and AChR start at the age of 18 and 22+ months in mice (Li et al. 2011).
Studies show that mice running more in the wheel and train their muscles had an increase NMJ area and also old mice that had already fragmented NMJ could de-crease their percentage of fragments if they train their