Developmental neuroscienceAbnormalities in neuromuscular junction structure and skeletal muscle function in mice lacking the P2X2 nucleotide receptor
Section snippets
Animals
P2X2−/− mice were generated by introducing a deletion encompassing exons 2–11 into the mouse P2X2 gene (see Cockayne et al., 2005 for details).
Immunohistochemistry and histology
Four female wild-type and four P2X2−/− mice were killed by CO2 asphyxiation and death was confirmed by cervical dislocation according to Home Office (UK) regulations covering Schedule 1 procedures. All experiments conformed to the Royal Free and University College Medical School guidelines on the ethical use of animals; experiments were designed to
Results
P2X2−/− mice were fertile with no signs of gross pathology. We did not detect any significant differences in body mass (27.8 g±1.7 g, wild-type; 27.6 g±0.5 g, P2X2−/− mice). While differences in the muscle masses of wild-type and P2X2−/− extensor digitorum longus (10.9±0.7 mg, wild-type; 9.68±0.5 mg, P2X2−/−) and soleus muscles (9.1±0.44 mg, wild-type; 8.2±0.32 mg, P2X2−/−) were suggestive of muscle atrophy, values did not reach significance (P=0.15 for soleus muscle).
Discussion
Although ATP is well recognized as an important neurotransmitter in the CNS and peripheral nervous system mediating fast synaptic signaling (see Burnstock, 2007), the role of purinergic signaling in the formation and maintenance of synapses has not been fully investigated. In this study P2X2 receptor-deficient mice were used to demonstrate a role for ATP signaling in the formation of mature NMJs. Our results show that the normal expression of the P2X2 receptor protein on developing skeletal
Conclusion
In summary, we demonstrate that absence of the P2X2 receptor on skeletal muscle results in significant abnormalities in muscle structure and function. These effects can be explained most simply by proposing a role for the P2X2 receptor in the normal development of the NMJ. It is becoming increasingly clear that the development and maintenance of synapses is a complex process requiring a balance between stabilizing and de-stabilizing factors. A number of other factors have been shown to
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