Duchenne muscular dystrophy is caused by abnormalities in the protein dystrophin. In addition to severe fatal muscle disease patients with Duchenne dystrophy have a moderate cognitive impairment. Dystrophin and several smaller proteins made from the same gene occur in the brain. Some of these forms of dystrophin occur in neurons, and the absence of these forms from neurons which normally contain these proteins may contribute to mental retardation. Although the evidence is less compelling, other dystrophin isoforms appear to be localized to glia. These supporting cells of the nervous system have a variety of critical functions, and there is ample evidence that alterations in there function may also cause cognitive dysfunction. An alteration in one or more of the dystrophin isoforms is likely to cause cognitive impairment. However, specifically which proteins these are, where they are, that is in which cells, what is their function, and how they could contribute to mental retardation are not understood. This study focuses on a specific new dystrophin isoform, and will address these questions. This protein is presumed to be made from the dystrophin gene, is similar in some respects to dystrophin, and appears to be in the glial or supporting cells, especially in the olfactory nerves. The olfactory nerves are unusual in that they are the only connections within the brain that are renewed throughout life and can re-establish correct connections throughout life. It has been suggested that the unusual glial cells of the olfactory nerve may contribute to this unique capacity. The lack of this capacity in most of the brain is a major reason why """"""""functional recovery"""""""" after brain injury is so limited. This study will clone the gene for this olfactory protein, identify its mRNA, measure the amounts and location in different areas of the brain, and examine the location and types of cell which contain the protein. The final part of the project is to study what other proteins interact or associate with the olfactory dystrophin isoform. This information may shed light on both mental retardation and the recovery of connections in the central nervous system.
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