Canine centronuclear myopathy (CNM) is a relatively common condition in Labrador Retrievers that shares both clinical and pathological features with human centronuclear myopathies. These dogs could provide a naturally occurring model for related diseases in humans. Canine CNM is caused by a mutation in a gene called PTPLA. Little is known about this gene in mammals but it is strongly expressed in heart and skeletal muscle. The PTPLA protein is similar to a yeast protein that is involved in making special sorts of fats – in mammals these types of fats likely have an important role in formation and maintenance of cell membranes (including those which conduct impulses in muscle cells). Consequently, muscle weakness that occurs in affected dogs may occur in a similar way to that in human myotubular myopathies.

During the first part of this project we have sought to find out more information about the role of this gene in muscle cells – particularly during development. There are two different genetic messages and therefore two different proteins produced from the PTPLA gene in muscle and we have looked at the localisation of both of these in immature and more developed mouse muscle cells: both proteins are found in a certain structure (the endoplasmic reticulum) which is known to be important in fatty acid and protein production. Interestingly, the larger of the 2 proteins seems to be especially important in more mature skeletal muscle and the heart, whereas the shorter form is expressed in many cell types and immature muscle. We discovered that there is a gradual switch during development between the shorter to the longer form in muscle. This information (presented recently at the International Congress on Neuromuscular Diseases in Naples) raises further questions about the role of this gene in muscle development and in these diseases which we hope to answer in our further work.

If you are interested to read more about the research project that the Myotubular Trust is funding, and in an easy-to-understand format (with thanks to Dr Juliet Ellis) please download the PDF about Dr Richard Piercy’s research project.