Identification of a New Pmp22 Mouse Mutant and Trafficking Analysis of a Pmp22 Allelic Series Suggesting Protein Aggregates May Be Protective in Pmp22-Associated Peripheral Neuropathy

Microarrays are increasingly used to look at the gene expression profiles of cells or tissues and in this study we have used two separate microarray models to study the disease. Firstly nylon cDNA arrays were used on both a mouse and human model of the disease and then a new proteomic technology, the antibody array was used on the human model for comparison. Dissociated motor neurons were established from the spinal cord of the mouse models and total RNA was hybridised onto a nylon filter containing 24,000 cDNAs and representing over 90% of the mouse genome. Primary muscle cultures were established from patient and normal controls and validated as a model in which to study SMA. Total RNA was hybridised to a human filter also representing the majority of the sequenced human genome. Data was analysed and cluster analysis was performed. A number of expression changes were confirmed with Real Time PCR which occurred in both human and mouse samples. These included SMN itself, p53, a known binding partner and a recently identified splicing factor which has not previously been associated with SMA. Finally a novel technology, the antibody array, was used to compare the protein profiles of SMA and normal primary muscle cultures. This found up regulation of a number of transcription factors within the same pathway of action as p53. These results offer interesting insights into the molecular pathogenesis of SMA.