QUALITATIVE AND QUANTITATIVE VARIATIONS O F SOME PROTEINS FROM SPINAL-CORD AND MUSCLE IN SPINAL MUSCULAR-ATROPHY

The various types of childhood spinal muscular atrophy (SMA) represent a spectrum of clinical disorders resulting from the degeneration of m otor neurons (MN). The genetic defect has been recently localized to c hromosome 5q in the region 11.2-13.3. Under normal conditions, half of the motor neurons die during embryonic development while the remainin g 50 % survive to innervate muscle fibers and form neuromuscular junct ions. Numerous studies using in vivo and in vitro models have shown th at survival of MNs depends on the presence of trophic factors of neuro nal and muscular origin. However, at the present time, no molecular me chanisms can be proposed to account for the nature and the sequence of the interactions leading to the formation and maintenance of a functi onal neuromuscular junction. To gain a better understanding of the SMA disorders, an alternative to genetic studies consists in analyzing th e molecular mechanisms underlying this pathology. Variations in the ex pression of proteins, for instance, might reflect the pathological phe notype. We thought it possible to detect differences in the protein(s) which would correlate with the molecular deficit of childhood SMA. We , therefore, compared the patterns of human protein expression from no rmal controls and SMA spinal cord and muscle. Significant variations i n the expression of some proteins, which have been quantified by a com puterized Bio-Image electrophoresis system, ham been found In particul ar, two proteins, a and b (126 kDa and 112 kDa) which are very probabl y common to spinal cord and muscle show a marked increase of their exp ression in children with SMA. Two minor proteins are also of interest : c (35 kDa) in spinal cord and f (30 kDa) in muscle. They are found i n control material and are not detectable in the corresponding SMA tis sues. We are currently trying to identify these proteins in order to u nderstand,why their expression is altered in SMA. This will involve mi crosequencing and the preparation of monoclonal antibodies.