THE DISTRIBUTION OF SMN PROTEIN COMPLEX IN HUMAN FETAL TISSUES AND ITS ALTERATION IN SPINAL MUSCULAR-ATROPHY

Spinal muscular atrophy (SMA) is a common autosomal recessive neuromus cular disorder characterized by degeneration of motor neurons of the s pinal cord and muscular atrophy. SMA is caused by alterations to the s urvival of motor neuron (SMN) gene, the function of which has hitherto been unclear. Here, we present immunoblot analyses showing that norma l SMN protein expression undergoes a marked decay in the postnatal per iod compared with fetal development, Morphological and immunohistochem ical analyses of the SMN protein in human fetal tissues showed a gener al distribution in the cytoplasm, except in muscle cells, where SMN pr otein was immunolocalized to large cytoplasmic dot-like structures and was tightly associated with membrane-free heavy sedimenting complexes . These cytoplasmic structures were similar in size to gem. The SMN pr otein was markedly deficient in tissues derived from type I SMA fetuse s, including skeletal muscles and, as previously shown, spinal cord. W hile our data do not help decide whether SMA results from impaired SMN expression in spinal cord, skeletal muscle or both, they suggest a re quirement for SMN protein during embryo-fetal development.