Our ability to investigate the genetic basis of neuromuscular disease has entered a new era as advances in sequencing allow more rapid identification of underlying mutations. Mutations identified in patients can be moved quickly to model organisms, such as mice, for the detailed mechanistic studies not possible in patients. The number of available mouse models of neuromuscular disease is increasing constantly, as is the repertoire of available molecular genetics tools. By comparison, there is a relative lack of sophisticated tools for in vivo phenotypic characterization in mice with neuromuscular disease. In the clinic, electromyography (EMG) and nerve action potentials (NAP) data are routinely collected from patients for diagnosis and research. These measures of neuromuscular performance are particularly useful because they can be repeated and used to monitor progression or response to treatment over time. We propose to develop similar capabilities in mice by refining existing implantable technology that will allow longitudinal recording of EMG and NAP in untethered, freely moving mice.
The rate at which genetic mutations that cause neuromuscular disorders, such as Lou Gehrig's disease, can be identified has accelerated, but it requires much more time to understand the mechanisms that cause disease, and then develop treatments. Much of the work necessary to understand neuromuscular disease cannot be conducted in humans and therefore relies on model organisms such as the mouse. Studies in mice are critical, but are slowed somewhat by a relative lack of sophisticated tools for making measurements of neuromuscular performance in a conscious, normally behaving animal. Measurements of electrical activity in muscles and nerves are routinely performed in conscious humans, but these same measures are so technically difficult in small animals that they are effectively inaccessible to researchers. The work proposed here is aimed at refining existing miniature implantable devices for recording muscle and nerve electrical activity in awake, freely moving mice. The validation and transfer of this technology for research in mice will provide a new clinically relevant tool for study and evaluation of potential treatments of neuromuscular disorders.